The interface between systemic sclerosis (SSc) and cancer has offered valuable insights into our understanding of SSc disease pathogenesis. Defining SSc subgroups both temporally and serologically has been instrumental in stratifying cancer risk, with autoantibodies to RNA polymerase 3 (RNApol3), RNA polymerase I large subunit (RPA194), RNA Binding Region Containing 3 (RNPC3), and centromere identifying subgroups at increased or decreased risk of cancer. Clinically, improved subgrouping of SSc patients provides the opportunity to detect cancer at earlier stages of disease while increasing our efficiency of cancer assessment. Additional studies are needed to define the optimal approach to cancer screening in SSc, and validation studies in different cohorts will be needed to confirm all findings.