We present an interesting case of a 56-year-old Egyptian woman with high-grade urothelial carcinoma (HGUC) associated with schistosomiasis that appeared initially as low-grade (LGUC) disease on transurethral resection of the bladder tumor (TURBT). Areas of HGUC and tumor invasion were detected only after meticulous microscopic examination of the partial cystectomy specimen. Furthermore, there were no areas of squamous cell metaplasia identified. This case highlights one of the limitations of biopsy for determining cancer grade and stage. It also emphasizes that schistosomiasis may be associated with non-squamous cell forms of bladder cancer, the pathogenesis of which has not been fully elucidated.