It is fairly simple to differentiate between the Rough Endoplasmic Reticulum and the smooth Endoplasmic Reticulum. One key difference between the two is the presence of ribosomes on them. The Rough Endoplasmic Reticulum has ribosomes attached to it whereas the smooth Endoplasmic Reticulum does not. Another difference is that the Rough Endoplasmic Reticulum makes protein but the smooth Endoplasmic Reticulum makes lipids.