Two cases of acute promyelocytic leukemia with variant translocation involving 4 chromosomes are described. The karyotypes were 47,XX, +8,t(13;15;17;20)(q22;q22;q12;q13) and 46,XY,t(5;15;16;17)(q22;q22;p13;q12), respectively. Variant translocations in APL apparently do not follow any preferential routes since no recurrent breakpoint additional to those of chromosomes 15 and 17 has been found in any of the cases reported in the literature and in those described here. Moreover, it seems that the translocation of the RAR alpha gene from chromosome 17 to chromosome 15 is directly involved in the pathogenesis of the disease, while the reciprocal one is not, as demonstrated by variant translocations where 15q migrates to chromosomes other than 17.