Uterine leiomyosarcoma (LMS) is a deadly uterine smooth muscle tumor. Leiomyoma with bizarre nuclei (LM-BN) and fumarate hydratase-deficient leiomyoma (FH-LM) are benign uterine smooth muscle tumors with remarkable nuclear atypia. FH-LM is driven by biallelic inactivation of fumarate hydratase, but the pathogenesis of LMS and LM-BN remains largely unknown. Both LMS and LM-BN are genomically unstable tumors and share many similar chromosomal copy number alterations (CNA). To further investigate the molecular relationship between LMS and LM-BN, we herein assess the oncogenic-related single nucleotide polymorphisms (SNPs) by whole genome sequencing analysis in LMS, LM-BN and FH-LM. Our unbiased approach revealed the existence of heterogeneity in genotype profiles within a tumor subtype, and the unbiased clustering analysis may benefit further selection of informative SNPs. Using EMOGI we further selected 14,358 SNPs annotaed on the predicted 165 novel cancer cadidate genes and identified a small set of 140 SNPs using random forest models. The SNP profiles revealed a higher proportion of loss of heterozygosity (LOH), or homozygote alternative were enriched in most LMS and a portion of the LM-BN tumors, but not in FH-BN. This study further provides important molecular evidence for a link between LMS and LM-BN.