Renal medullary carcinoma is a recently described aggressive neoplasm of the kidney. With the exception of 2 patients, all other reported cases have been associated with sickle cell hemoglobinopathies, mainly sickle cell trait and hemoglobin SC disease. Renal medullary carcinoma is a highly malignant tumor with evidence of angiolymphatic and distant metastasis at the time of diagnosis. No specific genetic abnormality has been identified in this neoplasm despite its close association with a genetic disease. We describe 2 cases of renal medullary carcinoma, one associated with hemoglobin SC disease, and the other with what we believe to be the first reported case associated with sickle cell disease.