8589 Background: Spindle cell melanoma and its variant desmoplastic melanoma (DM) are a rare but distinct subset of malignant melanomas, and their genomic aberration have not been reported. Insight into these aberrations can help guide management, which has also not been outlined. We examined the frequencies of BRAF , NRAS and KIT mutations in spindle cell melanoma in this retrospective study. Methods: We searched in our institutional database at The University of Texas M.D. Anderson Cancer Center for patients with a diagnosis of pure spindle cell type melanoma (excluding the mixed type with spindle cells) whose tumors were analyzed for BRAF (exon 15 hotspot), NRAS (exons 1 and 2 hotspots) and KIT (exons 11, 13 and 17) mutation. The genomic sequencing analyses were performed with pyrosequencing, a PCR-based DNA sequencing technique. Results: We identified 24 patients with spindle cell melanoma, of which 10 patients had a diagnosis of DM, whose tumor were analyzed for at least 1 of the 3 genes. The mean age of the patients was 57 years, and fifteen (62.5%) of these patients were male. The median Breslow thickness was 2.8 mm, and the most common site of the primary melanoma was the trunk, followed by the head and neck region. BRAF, NRAS and KIT genomic sequencing was performed successfully in 20, 18 and 14 patients, respectively. Among the 20 melanomas with completed BRAF sequencing analysis, 6 (30%) harbored a mutation, of which 5 (83%) were V600E and 1 (17%) was V600R. None of the melanomas harbored NRAS or KIT mutation. Conclusions: This is the first report to note the genomic aberrations in spindle cell melanoma. As in the other common types of melanoma, V600 BRAF mutation is the most common mutation in spindle cell melanoma. However, unlike the other common subtypes, we did not identify any NRAS in the 18 patients analyzed. Also, despite the association of DM with intense sun damage, KIT mutation was not seen in 14 patients, 5 of which were DM. Larger studies are needed to further validate the mutational prevalence of BRAF, NRAS and KIT, but these latter two are likely to be very rare or absent. This information can hopefully lead to more prudent management and treatment decisions.