In humans, soft tissue sarcomas are rare cancers with many unique histologic subtypes. Therapeutic clinical trials evaluating novel treatments are limited by small sample sizes and disease heterogeneity, limiting opportunities to improve patient outcomes. In this chapter, we will focus on sarcomas arising from the soft tissues. Canines spontaneously develop soft tissue sarcoma (STS) more commonly than humans, importantly while living in the same environment as their owners. As such canines with STS provide the opportunity to study the cancer genetics and perform clinical trials in real-world conditions with spontaneous tumors. The spontaneous dog STS model provides a unique opportunity to advance device or drug development. Canine trials can be done as part of preclinical development for more informed human clinical trials, or they can be run in parallel with human clinical trials, providing more power due to larger canine patient populations. This chapter will provide a synopsis of human and canine STS and demonstrate how the canine model may play a crucial role in the development of novel therapeutics and treatment of humans with STS.