This issue of Surgical Pathology Clinics is devoted to Soft Tissue Tumors, the first in this series was presented in 2011. This issue addresses the most difficult diagnostic challenges and focuses on differential diagnosis in soft tissue tumors. Each presentation is accompanied by abundant histologic slides to display the diagnostic differences. Additionally, authors selected two to five diagnoses they find can be particularly difficult, with an emphasis on how to approach such lesions on biopsy samples where relevant and the role of ancillary studies. Topics include coverage of diagnostically challenging: Vascular lesions; Retroperitoneal “Fatty” tumors of adults; Smooth muscle neoplasms; Chondro-osseous lesions of soft tissue; Pediatric tumors; Epithelioid tumors; Spindle cell neoplasms of the retroperitoneum; and Peripheral nerve sheath tumors. Also presented are: Non-mesenchymal mimics of benign and malignant soft tissue tumors; Soft tissue tumors with overlapping molecular findings; Recently characterized soft tissue tumors; Benign mimics of sarcoma; Advances in molecular methods in the analysis of soft tissue tumors and therapeutic implications; and Myoepithelial tumors: an update. Leona Doyle and Karen Fritchie lead this issue of experts in soft tissue pathology.