The MYB gene encodes a protein with three HTH DNA-binding domains that functions as a transcription regulator. This protein plays an essential role in the regulation of hematopoiesis. The MYB gene may be aberrently expressed or rearranged or undergo translocation in leukemias and lymphomas, and is considered to be an oncogene. Alternative splicing results in multiple transcript variants. The MYB gene is expressed predominantly in immature progenitor cells of all hematopoietic lineages and is highly expressed in most leukemias and in some solid tumors. Translocations affecting MYB have been detected in T-cell acute lymphoblastic leukemia (T-ALL) and adenoid cystic carcinoma (ACC). In ACC a recurrent translocation t(6;9) (q22-23;p23-24) is found in about one third of karyotypically abnormal cases. The translocation results in the fusion of the two transcription factor genes MYB and NFIB (nuclear factor I/B) which leads to enhanced expression of the MYB-NFIB fusion protein. The detection of MYB rearrangements using FISH might represent a powerful adjunctive diagnostic tool useful in the differential diagnosis of ACC.