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Renal medullary carcinoma (RMC) is a rare and aggressive malignant epithelial neoplasm of the kidney. It almost exclusively affects children and young adults with a sickle cell trait or sickle cell disease. The majority of RMC patients present with widely disseminated disease at the time of diagnosis. Herein, we report two cases of young African-American patients with history of sickle cell trait, hematuria and renal mass, who present with malignant right pleural effusions. The cytology of pleural effusion reveals predominantly clusters and individual tumor cells. The tumor cells show high nuclear to cytoplasmic (NC) ratios and large nuclei with nuclear pleomorphism, nuclear grooves, and prominent single or multiple nucleoli. The cytoplasm is dense with a vacuolated and two-tone appearance. Surgical specimens of renal mass and lymph node show features of RMC.Metastatic RMC to the serous cavity is rare and may present a diagnostic dilemma since it may mimic a poorly differentiated adenocarcinoma or other high-grade malignant neoplasms. RMC should be considered in the differential diagnosis in young patients with a renal mass, particularly in those with history of sickle cell trait or sickle cell disease.