Inverted papillomas of the bladder are uncommon benign neoplasms characterized by endophytic growth of urothelial cells as anastomosing cords, displaying minimal cytologic atypia. Reports of inverted papilloma associated with urothelial carcinoma or urothelial carcinoma arising within inverted papilloma highlight the difficulties in evaluating urothelial lesions with inverted growth patterns. Within the spectrum of findings in inverted papilloma, vacuolization and foamy (xanthomatous-appearing) cytoplasmic changes have not been previously reported. In the current study, we present 5 novel cases of inverted papilloma involving 2 men and 3 women ranging in age from 48 to 88 years, who presented with microhematuria (n = 3) or irritative symptoms (n = 2). Cystoscopically, the lesions were polypoid (n = 3), pedunculated (n = 1), or solid (n = 1), measured between 0.7 and 2.5 cm, and were all located at the trigone or bladder neck. Morphologically, all cases had some component of usual inverted papilloma along with areas displaying foamy or vacuolated cytoplasm encompassing 30% to 90% of the lesion. These "clear cells" were seen both in distinct regions within the biopsy and, more frequently, intermingled with usual inverted papilloma cells. In 3 of 5 cases, these findings were sufficiently unusual to cause confusion with urothelial carcinoma. The diagnostic dilemma encountered in these cases of inverted papilloma with foamy or vacuolated cytoplasm warrants their distinction from other benign and malignant urothelial lesions with inverted growth and/or clear cell features.