Cathepsin D (CatD) and tenascin C (Tn-C) have been implicated in invasion and metastasis of carcinomas. However, little is known about CatD and Tn-C distribution in mesenchymal tumors. Therefore, we aimed to investigate the expression of Tn-C and CatD in adipocytic tumors. Tn-C and CatD expressions in 27 lipomas, 5 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLS) and 11 liposarcomas (LS) were evaluated by immunohistochemistry and scored semiquantitatively. CatD expression was higher in ALT/WDLS than in lipomas (p<0.001), and higher in LS than in ALT/WDLS (p=0.009). Stromal Tn-C expression was higher in ALT/WDLS than in lipomas (p=0.02), but no difference was observed between ALT/WDLS and LS (p>0.05). These results indicate that Tn-C and CatD may be markers of locally aggressive or malignant behavior in adipocytic tumors.