Klinefelter syndrome (KS), a 47,XXY chromosomal abnormality, has been shown to 
be associated with a number of malignancies, but has not been linked to acute 
leukemias to date. We present a case of a 54-year-old male diagnosed with acute 
myeloid leukemia (AML) with monocytic differentiation, whose cytogenetic and 
subsequent FISH analyses revealed a constitutional 47,XXY karyotype. We also 
review and discuss relevant prior literature.