In situ adenocarcinoma of the bladder has not been well studied. Only one other case not associated with infiltrating adenocarcinoma has been reported in the literature. We identified 19 biopsies of in situ adenocarcinoma of the bladder without concurrent infiltrating adenocarcinoma or villous adenoma from the surgical pathology files of the Johns Hopkins Hospital between May 1984 and July 2000. The majority of patients (89%) were seen in consultation. The mean age at diagnosis was 70.4 years (range 48-88 years) and 79% were male. None of the patients developed a pure infiltrating adenocarcinoma; however, two patients had invasive urothelial carcinoma with focal glandular differentiation on prior or subsequent specimens. Two cases were pure in situ adenocarcinoma and 10 were seen with carcinoma in situ and/or papillary transitional cell cancer without invasion. Most patients (74%) had invasive carcinoma on either concurrent or subsequent specimens (five small cell and nine transitional cell [four micropapillary]). The majority (84%) of in situ adenocarcinomas were papillary, often seen in combination with either cribriform or flat architecture. In most cases the in situ adenocarcinoma was the predominant component when it was present with another in situ urothelial carcinoma. Seventy-nine percent of in situ adenocarcinomas showed >5 mitoses/10 HPF and 42% showed >10 mitoses/10 HPF. Moderate to severe nuclear pleomorphism was seen in 84% of cases. All cases showed apoptosis, and only one case showed focal necrosis. Seven patients were treated with cystectomy within 2-12 months. Of the other 12 patients, 10 were followed for a mean of 19.3 months (range 1-62 months). Ten (52%) patients were treated with bacille Calmette-Guérin, of whom four had no residual tumor on subsequent biopsy or cystectomy specimens. Three patients developed metastatic disease. In situ adenocarcinoma is a rare lesion that has a high incidence of association with small cell and micropapillary transitional cell carcinomas. When identified, in situ adenocarcinoma may indicate subsequent development of specific types of prognostically poor invasive carcinomas.