Soft tissue neoplasms are diagnostically challenging, although many advances in ancillary testing now enable accurate classification of fine-needle aspiration biopsies by detection of characteristic immunophenotypes (including protein correlates of molecular alterations) and molecular features. Although there are many useful diagnostic immunohistochemical markers and molecular assays, their diagnostic utility relies on correlation with clinical and morphologic features, judicious application, and appropriate interpretation because no single test is perfectly sensitive or specific. This review discusses applications of ancillary testing for commonly encountered soft tissue neoplasms in cytopathologic practice in the context of a pattern-based approach.