Six patients from the clinical cytogenetics laboratory identified as having the normal variant dup(15)(q12) were further evaluated using fluorescence in situ hybridization (FISH). The purpose of this study was to ascertain whether any of the Prader Willi Angelman Chromosome Region (PWCR and ANCR, respectively) loci were duplicated in these patients. The results indicated that the patients could be categorized into two groups. The first group showed no duplication of the PWCR ANCR loci and appeared to belong to the dup(15)(q12) class which is phenotypically silent and is therefore called the normal variant. The second group also showed no duplication of the PWCR/ANCR loci. but had a large alpha satellite variant with D15Z. It is hypothesized that these patients do not have a duplication of 15q12 but rather a centromeric variant which mimics the dup(15)(q12). This study confirms the importance of evaluating apparent variations in the proximal region of chromosome 15 with FISH.