The ETV6 gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. The ETV6 gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. More than 40 translocations with ETV6 involvement have been reported in diverse types of hematological and non-hematological malignancies. The ETV6-NTRK3 gene fusion resulting from the t(12;15)(p13.2;q25) translocation was found to be characteristic for mammary analogue secretory carcinoma (MASC) of the salivary glands. Since MASC morphologically mimics other neoplasms, the detection of ETV6 rearrangements may be helpful for the differential diagnosis of MASC.