Smooth muscle neoplasms of the urinary bladder are relatively rare. We report the largest series to date examining the clinicopathologic features of leiomyomas and leiomyosarcomas of the bladder. This study sought to clarify several issues relating to smooth muscle neoplasms of the urinary bladder: (1) How to distinguish leiomyomas of the bladder from normal muscularis propria on transurethral resection (TUR) specimens; (2) Whether symplastic leiomyomas can be diagnosed in the bladder; (3) Can leiomyoma be definitively diagnosed on biopsy or TUR without the risk of there being unsampled leiomyosarcoma; and (4) Is the grade of leiomyosarcoma seen on biopsy or TUR heterogeneous and hence possibly not representative of the true grade. Thirty-one leiomyomas and 20 leiomyosarcoma cases of urinary bladder from 3 tertiary care medical centers were examined. Leiomyosarcoma cases were subdivided into low-grade and high-grade based on mitotic count (> or =5/10 HPF) and nuclear atypia. The mean age of the patients with leiomyoma and leiomyosarcoma was 52 and 58, respectively. The M:F ratio was significantly higher in patients with leiomyosarcoma (2:1) compared with leiomyoma (1:3), p<0.005. The specimen consisted of 20 TUR and 11 transurethral biopsies (TUBx) for leiomyomas, and 10 TUR, 3 TUBx, 5 cystectomies (Cyst), and 2 partial cystectomies (pCyst) for leiomyosarcomas. LEIOMYOMAS: Notable features in leiomyomas were hyalinization (7/31), degenerative atypia (7/31), necrosis (4/31), myxoid changes (2/31), and focal fatty metaplasia (1/31); although no surface ulceration was identified. Clinical follow-up was available for 24 patients (12 to 108 mo; mean 36 mo); 4 lost to follow-up and 3 recent cases. Two patients had repeat TUR within a year of the initial diagnosis with the same bland leiomyoma on histology, probably reflecting persistence of earlier unresected tumor as opposed to recurrent tumor. None of the patients were diagnosed with leiomyosarcoma on follow-up, including 7 cases with degenerative atypia. LEIOMYOSARCOMA: Of the 20 leiomyosarcomas, 8 were classified as low-grade and 12 as high-grade sarcomas. Histologic features included epithelioid morphology (5/20; 1 entirely epithelioid), tumor cell necrosis (11/20), and mucosal ulceration (7/20). Infiltration into the muscularis propria was seen predominantly as a nodular growth pattern with some cases exhibiting an irregular infiltrative pattern (6/10 with evaluable borders); an infiltrative pattern was not restricted to high-grade lesions. Lesional heterogeneity was present in only 1 case on the same specimen, which showed both low-grade and high-grade areas. Another case was low grade on TUR, yet high grade at cystectomy. None of the cases of leiomyosarcomas had areas histologically resembling leiomyoma. Clinical follow-up was available for 15 patients with leiomyosarcoma (11 to 144 mo; mean 47 mo); 3 lost to follow-up and 2 recent cases. Only 1 patient with low-grade sarcoma experienced 2 local recurrences treated only by TUR and is currently free of disease. Disease-related mortality was significantly higher in patients with high-grade compared with low-grade leiomyosarcomas (50% vs. none, respectively; P<0.001). Leiomyoma (including symplastic leiomyoma) may be diagnosed on TUR without risk of underdiagnosing unsampled leiomyosarcoma. High-grade leiomyosarcomas are highly aggressive neoplasms compared with low-grade leiomyosarcomas; in most cases grade can be accurately determined on TUR.