The objective of this study was to review the clinicopathological features of seven patients presenting with well-differentiated liposarcoma (WDL), which was associated with subcutaneous lipoma. From 1980 through 2002, 34 individuals displaying WDL were treated in our institutions. Lipoma was observed in seven of these 34 patients (five men and two women, mean age of 66.7 years). The rate of co-existence of lipoma in WDL [20.6% (7/34)] cases was significantly higher than the corresponding rate in the other liposarcoma subtypes [2.5% (1/40)]. Immunohistochemically, cdk4 was positive in all WDLs (100%). ki-67 was positive in 57.1% (4/7) and mdm2 and p53 were positive in 14.5% (1/7) of the WDL cases. Weak cdk4 immunoreactivity was detected in two lipomas. All lipomas were negative for mdm2, p53 and ki-67. Comparison of the expression profile in these malignant and benign tumors, which had arisen in identical genetic backgrounds, confirmed the involvement of these proteins, especially cdk4, in the tumorigenesis process of WDL.