Terminally differentiated rhabdomyoblasts are common after or during therapy for rhabdomyosarcoma (RMS). Case reports have suggested that their presence after therapy does not indicate a poor prognosis, but significance and relationship to outcome has not been systematically studied. Management of patients with this finding can cause confusion. Slides and pathology reports from 44 patients with bladder/prostate RMS treated on Fourth Intergroup Rhabdomyosarcoma Study were examined by a pathologist experienced in RMS, and findings compared with institutional reports. Details regarding patient characteristics, outcome, and management were reviewed. Outcome of patients with various pathologic findings was assessed. One of 10 patients with only mature rhabdomyoblasts at their last procedure recurred, versus 4 of 17 patients with viable tumor and 2 of 17 patients with no viable tumor and no rhabdomyoblasts. Sixteen of 42 cases reviewed had results differing from our review. Mature rhabdomyoblasts are a discrete entity which may not be predictive of recurrence, but should be evaluated by a pathologist experienced with this entity. The presence of mature rhabdomyoblasts at the end of therapy for bladder/prostate RMS does not justify radical surgery. Sequential biopsies are subject to sampling error and should only be performed in the context of protocol-directed therapy to avoid unnecessary radical surgeries.