Process for the preparation of chondroitin sulphate sodium salt in which all the N-acetyl-D-galactosamine units in the same polysaccharide chain are monosulphated either randomly or at the 4- or 6- position, said process comprising the following steps: a. transformation of chondroitin sodium salt into its free acid or a salt thereof with a quaternary ammonium cation selected from tetramethylammonium, tetraethylammonium or tetrabutyl-ammonium, or into the pyridinium salt or the methyl ester; b. reaction of the compound obtained in step a) with an orthoester of formula RC(OR 1) 3, in which R is selected from hydrogen, methyl, ethyl or phenyl and R 1 is selected from methyl or ethyl, in the presence of acid catalysis, to give a compound in which the repeating disaccharide unit present in chondroitin has the formula I in which R and R1 are as defined above; c. protection of the hydroxy groups at the 2'- and 3'- positions of the glucuronic acid units of the compound obtained in the previous step by reaction with an anhydride of formula (R 2 CO) 2 O in which R 2 is selected from methyl, ethyl or propyl, in the presence of pyridine or an organic tertiary base selected from triethylamine or triisopropylamine and of 4-dimethylaminopyridine (DMAP), to give a compound in which the repeating disaccharide unit present in chondroitin has the formula II in which R, R 1 and R 2 are as defined above; d. rearrangement of the orthoester functionality present in the product obtained in step c) with an organic water-soluble acid to give an ester derivative in which the repeating GalNAc units in the polysaccharide consist of triacyl derivatives having formula IIIa or IIIb in which R and R 2 are as defined above; e. mono-sulphation of the compound obtained in step d) followed by removal of the O-acyl groups present in compounds IIIa and IIIb obtained in the previous step. a. transformation of chondroitin sodium salt into its free acid or a salt thereof with a quaternary ammonium cation selected from tetramethylammonium, tetraethylammonium or tetrabutyl-ammonium, or into the pyridinium salt or the methyl ester; b. reaction of the compound obtained in step a) with an orthoester of formula RC(OR 1) 3, in which R is selected from hydrogen, methyl, ethyl or phenyl and R 1 is selected from methyl or ethyl, in the presence of acid catalysis, to give a compound in which the repeating disaccharide unit present in chondroitin has the formula I in which R and R1 are as defined above; c. protection of the hydroxy groups at the 2'- and 3'- positions of the glucuronic acid units of the compound obtained in the previous step by reaction with an anhydride of formula (R 2 CO) 2 O in which R 2 is selected from methyl, ethyl or propyl, in the presence of pyridine or an organic tertiary base selected from triethylamine or triisopropylamine and of 4-dimethylaminopyridine (DMAP), to give a compound in which the repeating disaccharide unit present in chondroitin has the formula II in which R, R 1 and R 2 are as defined above; d. rearrangement of the orthoester functionality present in the product obtained in step c) with an organic water-soluble acid to give an ester derivative in which the repeating GalNAc units in the polysaccharide consist of triacyl derivatives having formula IIIa or IIIb in which R and R 2 are as defined above; e. mono-sulphation of the compound obtained in step d) followed by removal of the O-acyl groups present in compounds IIIa and IIIb obtained in the previous step.