Hemophagocytic syndrome (HS) is a severe and acute proliferative process of histiocytes, often associated with infection or malignancy. No consistent clonal abnormality has been reported in HS. We report a case of a child presented with HS, who progressed later to acute myeloid leukemia (AML)-M4, associated with a clonal evolution, from normal to a complex karyotype consisting of t [7:17] and deletions in chromosomes 7, 17, and 5. This is the second report of involvement of 7q rearrangement in a child with HS that has progressed to AML. Additional studies are required to establish the association reported here, between HS with progression to AML and chromosome rearrangements that involve chromosome 7q.