BackgroundCore needle biopsy (CNB) has been suboptimal in the subclassification and grading of mesenchymal tumors. Recent advances in molecular diagnostics have shown promise in improving this area. The institutional experience with CNBs of soft tissue lesions on cytology cases and correlated histologic follow-up has been evaluated. It also addressed the advantageous use of ancillary techniques, including immunohistochemistry and molecular studies. MethodsArchived cytologic CNB material and reports of patients with soft tissue lesions were retrieved and CNB results with final resection results were compared. Cases were re-reviewed and data were analyzed with descriptive statistics. ResultsFrom archived data, 215 cases were extracted of 99 female and 116 male patients (mean [range] age, 59.9 [12-95] years). Categories were malignant (n=157), suspicious (n=16), and benign (n=42). In total, 161 (74.9%) had subsequent surgical resection130 were malignant; 8, suspicious; and 23, benign. Of the malignant or suspicious cases, 138 had follow-up histologic resections, with 97.9% concordance. The most common malignant tumor was liposarcoma (n=41; 29.7%), followed by undifferentiated pleomorphic sarcoma (30; 21.7%). Of benign tumors, 23 (54.8%) had follow-up surgical resection. Low-grade gastrointestinal stromal tumor was the most common benign tumor (26.1%), followed by fibromatosis (21.7%). Cytohistologic correlation for all categories showed 96.9% concordance. Molecular ancillary studies correctly classified malignant tumors in 37 (26.8%) of the 138 cases. ConclusionCNB is a reliable modality for evaluating soft tissue neoplasms, with high histologic concordance rate. Diagn. Cytopathol. 2016;44:291-298. (c) 2016 Wiley Periodicals, Inc.