Well-differentiated liposarcomas (LPS) are cytogenetically very complex, characterized by giant marker chromosomes, ring chromosomes, and telomeric associations. We report a case of well-differentiated LPS in which the only cytogenetic anomaly was an additional giant marker. In an attempt to identify the origin of this marker, centromeric probes (chosen on the basis of the morphology of the marker) to chromosomes 1,2,3,4,6,7,8,9,10,11,12,16,17, and X and a shared satellite probe for chromosomes 1,5, and 19, were used with fluorescence in situ hybridization (FISH). This was successful at eliminating certain chromosomes as candidates for centromeric trisomy but could not identify the origin of the marker. This case is unusual in that it does not conform to the typical cytogenetic pattern for well-differentiated LPS and is the first known example with an apparently normal diploid karyotype with only one additional change.