The distinction of myeloproliferative disease (MPD) from leukemoid reactions due to reactive causes can be difficult. In the presence of simultaneous occurrence of MPD and an established infection, only the demonstration of a clonal marker or prolonged observation can substantiate the diagnosis. We present three cases of MPD presenting as leukemoid reaction due to disseminated hepatosplenic mycobacterial sepsis. There appeared to be an association between MPD and reduced resistance to mycobacterial infection. Clinicians and hematologist should be aware of such a predisposition and possible dual pathology for proper diagnosis, therapy and monitoring of both the infection and the myeloproliferation.