In this work, we undertake a comparative mass spectrometry-based proteomic analysis of intravenous leiomyoma (IVLM) and other smooth muscle tumours (uterine leiomyoma (uLM), soft tissue leiomyoma (stLM) and benign metastatic keiomyoma (BML). By utilising sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS), we quantified >2,400 proteins from FFPE samples and demonstrate that at the protein level, IVLM is characterised by the unique co-regulated expression of splicing factors that comprise the spliceosome.