The chemotherapeutic regimen melphalan, prednisolone, and thalidomide (MPT) is the standard of care for symptomatic multiple myeloma patients who are not eligible for high dose chemotherapy followed by autologous stem cell therapy. Lenalidomide, a newer thalidomide derivative, is 300 times more potent than thalidomide. Combined therapy using melphalan, prednisolone, and lenalidomide (MPL) is very effective with many advantages. We report here one rare adverse effect, i.e., intrahepatic cholestasis related to lenalidomide, in two patients out of a total of 65 newly diagnosed cases of multiple myeloma receiving MPL regimen in our series. As the use of lenalidomide will increase in the future for multiple myeloma and other diseases, clinicians should be aware of this entity.