Nonrandom reciprocal translocations involving chromosomes #15 and #17 are characteristic anomalies in a great majority of cases of acute promyelocytic leukemia (APL). Other complex translocations in APL that invariably involve chromosome #17 also have been described. We describe a patient with clinical and morphologic characteristics of APL but with a previously undescribed acquired karyotype, t(X;15)(p11;q22). This is the first translocation in APL described in which chromosome #17 is not involved. Although a comparative structure/function analysis of potentially relevant genes to the translocation breakpoints in both t(X;15) and t(15;17) APL showed no major alterations, the enhanced expression of the c-Ki-ras oncogene observed in t(X;15) APL supports the concept of heterogeneity in APL at the cytogenetic and molecular levels.