A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs comprising: (a) adding processed tumor fragments from a tumor resected from a patient into a closed system to obtain a first population of TILs; (b) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for 3-14 days to obtain the second population of TILs wherein the transition from step (a) to step (b) occurs without opening the system; (c) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for 4 to 6 days to obtain the third population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (b) to step (c) occurs without opening the system; (d) splitting the third population of TILs into a first plurality of five or less sub-populations of TILs, each sub-population comprising at least 1.0×10 9 TILs, and performing a third expansion of the first plurality of sub-populations of TILs by supplementing the cell culture medium of each sub-population of TILs with additional IL-2, optionally OKT-3, to produce a second plurality of sub-populations of TILs, wherein the second plurality of sub-populations of TILs comprise a therapeutic population of TILs, wherein the third expansion is performed for 5 to 7 days, wherein the third expansion for each sub-population is performed in a closed container providing a third gas-permeable surface area, and wherein the transition from step (c) to step (d) occurs without opening the system; (e) harvesting the therapeutic population of TILs obtained from step (d), wherein the transition from step (d) to step (e) occurs without opening the system; and (f) transferring the harvested TIL population from step (e) to an infusion bag, wherein the transfer from step (e) to (f) occurs without opening the system. (a) adding processed tumor fragments from a tumor resected from a patient into a closed system to obtain a first population of TILs; (b) performing a first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed container providing a first gas-permeable surface area, wherein the first expansion is performed for 3-14 days to obtain the second population of TILs wherein the transition from step (a) to step (b) occurs without opening the system; (c) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for 4 to 6 days to obtain the third population of TILs, wherein the second expansion is performed in a closed container providing a second gas-permeable surface area, and wherein the transition from step (b) to step (c) occurs without opening the system; (d) splitting the third population of TILs into a first plurality of five or less sub-populations of TILs, each sub-population comprising at least 1.0×10 9 TILs, and performing a third expansion of the first plurality of sub-populations of TILs by supplementing the cell culture medium of each sub-population of TILs with additional IL-2, optionally OKT-3, to produce a second plurality of sub-populations of TILs, wherein the second plurality of sub-populations of TILs comprise a therapeutic population of TILs, wherein the third expansion is performed for 5 to 7 days, wherein the third expansion for each sub-population is performed in a closed container providing a third gas-permeable surface area, and wherein the transition from step (c) to step (d) occurs without opening the system; (e) harvesting the therapeutic population of TILs obtained from step (d), wherein the transition from step (d) to step (e) occurs without opening the system; and (f) transferring the harvested TIL population from step (e) to an infusion bag,