Background: Understanding the genetic basis for the molecular classification of Sinonasal Undifferentiated Carcinoma (SNUC) based on SMARCB1 may improve our understating regarding the nature of the disease. The objective of the study was to compare the genetic profile of SMARCB1-retained (SR-SNUC) and SMARCB1-deficient SNUC (SD-SNUC). Methods: Formalin-fixed, paraffin embedded tissue (FFPE) from treatment-naïve patients with SNUC were selected. Three cases of SR-SNUC, four cases of SD-SNUC, and four samples of non-tumor tissue (control samples) were selected. RNA sequencing was performed. Results: SR-SNUC had a higher number of variants (1 variant for every 15,000 bases) compared to SD-SNUC (1 variant every 29,000 bases). The ratio of missense to silent mutation ratio was higher for SR-SNUC (0.8) as compared to SD-SNUC (0.7). Approximately 1500 genes were differentially expressed between SR-SNUC and SD-SNUC. The genes that had a higher expression in SR-SNUC included TPD52L1, B3GNT3, GFY, TJP3, ELL3, CYP4F3, ALDH3B2, CKMT1B, VIPR1, SLC7A5, PPP2R2C, UPK3B, MUC1, ELF5, STY7 and H2AC14. The gene that had a higher expression in SD-SNUC was ZFHX4. Most of these genes were related to either protein translation or immune regulation. The most common (n=3, 75%) mechanisms of loss of SMARCB1 gene in SD-SNUC was loss of heterozygosity. Conclusion: RNA sequencing is a viable and informative approach for genomic profiling of archival SNUC samples. Both SMARCB1-retained and SD-SNUC were noted to have distinct genetic profiles underlying the molecular classification of these diseases.