345 Background: Bladder cancer is a rare entity in the pediatric population making it difficult to define surveillance protocols and long term outcomes. Notably, most pediatric tumors are low grade and non-muscle invasive and do not recur. In order to determine the source of the different natural history between pediatric population and adults, we hypothesized that pediatric bladder cancer may potentially stem from different molecular pathways than its adult form. Our main objective was to study the molecular pathogenesis in this rare disease using immunohistochemical (IHC) and mutational analysis of the main known genes involved in bladder cancer. Methods: Paraffin-embedded tissue slides of bladder tumors from three pediatric patients were retrospectively identified from our institution's pathology archives (1990-present) and re-evaluated. Clinical data was reviewed. FGFR3, H-RAS, and PI3K mutational analysis of the most well-known mutated spots was conducted by PCR amplification and Sanger sequencing. IHC analysis was conducted using antibodies against p53, Pten, Rb, EGFR, Her2Neu and ki-67. Results: Two patients had low-grade Ta disease, whereas the other tumor was classified as a Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP). None of the lesions recurred. Two patients were female and one was male. The ages at diagnosis were 13, 11, and 17, with a mean follow-up of 5.2 years (Range: 1.5-8.0 years). All specimens showed H-RAS G12V mutation, whereas they were characterized by wild-type FGFR3 and PI3K. Nuclear p53 was not detected, whereas PTEN and Rb expression were maintained. EGFR was homogenously expressed in the three cases, and Her2Neu was negative. The proliferation rate analyzed by Ki-67 expression was very low in all cases (<5%). Conclusions: Pediatric tumors may arise from a pathway that is not initiated by FGFR3 or p53 mutations, but by H-RAS mutations. This distinction may explain the relatively few recurrences seen in the pediatric population. Molecular investigation of larger series of pediatric tumors is warranted, and will aid in determining the surveillance and the clinical follow up, if any, needed in this rare entity.