Urothelial carcinoma of the bladder with osteoclast-like giant cells (UCOGCs) is rare among the subtypes of poorly differentiated urothelial carcinoma. Its clinical significance and optimal treatment are unknown, and few reports on genomic analysis of UCOGCs have been reported. Detailed analysis including genetic analysis for rare type variants of cancer could be a foothold for further research. The present case describes the case of a 75-year-old man who presented with a non-papillary bladder tumor 56 mm in diameter showing gross hematuria and pain on voiding. Following transurethral resection of the bladder tumor, the pathological diagnosis was invasive UCOGCs. Neoadjuvant chemotherapy and radical cystectomy were performed with the resected tumor pathologically diagnosed as invasive UCOGCs, high grade, pT3b, pN1. The present study also analyzed the genomic features using a cancer panel test. The panel test noted six gene alterations (
PIK3CA
p.E542K,
HRAS
p.G13R,
ARAF
copy number amplification,
CDKN2A
copy number loss,
TP53
p.E285V,
ARID1A
p.S90Pfs*11) and telomerase reverse transcriptase (
TERT
) promoter variant. Accumulation of knowledge from molecular-based testing is anticipated to determine precise treatment for rare cancer.