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Objective The aim of this study is to assess the association between clinical and radiological features as well as of isocitrate dehydrogenase 1 and 2 ( IDH 1,2) mutations with outcome in head and neck chondrosarcomas. Study Design Retrospective study. Setting Tertiary referral center. Methods Clinical, histological, and molecular data of patients with head and neck chondrosarcomas treated by surgery were collected. Results Forty-six patients were included. The mean age at diagnosis was 56 years (range, 17-78). The tumor originated from the skull base (52.2%), facial bones (28.2%), or laryngotracheal area (19.6%). At last follow-up (median 52.5 months), 38 patients were alive, 30 of which were disease free, whereas 8 had died, 4 of disease progression and 4 of other causes. Fourteen (30.4%) had local recurrence and 2 (4.3%) had lung metastasis. All cases were negative for cytokeratin AE1/AE3, brachyury, and IDH1 at immunohistochemistry, while Sanger sequencing identified IDH1/2 point mutations, typically IDH1 R132C, in 9 (37.5%) tumors arising from the skull base. Margin infiltration on the surgical specimen negatively affected the outcome, whereas no correlation was identified with IDH mutation status. Conclusions An adequate margin positively affects survival. IDH mutation status does not affect patient outcome.