Spindle cell liposarcoma (SCL) is a rare malignant adipose tissue tumor presently regarded as a variant of well-differentiated liposarcoma (WDLPS). While WDLPS is cytogenetically characterized by the presence of supernumerary ring or giant chromosomes containing MDM2 amplification, data concerning the genomic alterations of SCL are scarce. Here, we describe the molecular cytogenetic characterization of two SCL cases. In these two cases, we did not identify supernumerary ring or giant chromosomes containing 12q amplification or any other chromosome 12 rearrangement. Instead, we observed a partial or complete monosomy 7 as the sole anomaly or among a few additional simple numeric and structural abnormalities. Monosomy 7 is not usual in adipose tissue tumors. It has been described in myelodysplastic syndromes and acute myeloid or lymphoblastic leukemias, as well as in several benign or malignant solid tumors. Our data suggest that the loss of material from chromosome 7 might play a crucial role in the pathogenesis of some SCL probably through the inactivation of tumor suppressor genes located on chromosome 7. On the basis of cytogenetic and molecular findings, some SCL may constitute an independent entity rather than being regarded as variants of WDLPS.