The field of soft tissue pathology has experienced a tremendous expansion through the integration of molecular diagnostics as part of everyday clinical practice. Consequently, this has allowed the production of novel immunohistochemical markers corresponding to certain proteins expressed in these tumors. In this article, we will review known and novel immunohistochemical studies that can be applied to help practicing pathologists identify and diagnose these rare neoplasms, some of which are specific to certain genetic alterations.