Venous thrombosis is a well-recognized complication of lenalidomide therapy in patients with multiple myeloma, but its occurrence during the treatment of other hematologic malignancies is less well described. In this report, we detail the occurrence of corpora cavernosa thrombosis in a patient receiving lenalidomide for the therapy of myelofibrosis. This case highlights the need for clinical vigilance in patients who present with unusual symptoms during investigational therapy, and indicates that the occurrence of venous thrombosis complicating therapy with lenalidomide or related compounds is not isolated to patients with multiple myeloma.