Deletions of chromosome 6q are found in many types of cancer, including melanoma, prostate cancer, fibroadenomas, and carcinoma of breast and other sites. Chromosome 6q deletions are also commonly found in lymphoid malignancies such as acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), non-Hodgkins lymphoma (NHL), multiple myeloma (MM), mantle zone lymphoma (MZL), and Waldenström's macroglobulinemia (WM). These deletions may appear to be terminal or interstitial. In childhood B- and T-cell ALL a deletion of 6q is the hallmark of a neutral prognosis; however, it may be cytogenetically obscure or cryptic, requiring interphase FISH analysis. In adult ALL it indicates a favorable prognosis, but in CLL, B-cell small lymphocytic lymphoma (SLL), WM, and MM it has a poor prognosis. Since the deletion of 6q has prognostic implications and may be used to monitor residual disease, FISH analysis remains a valuable tool in treatment of these disorders. Using our three-color FISH probe cocktail for 6 centromere, 6q21 and 6q23, we began a validation series. We report the results of the first three patients in our laboratory with deletions of 6q in lymphoid malignancies using this cocktail.