Chronic myelomonocytic leukemia (CMML) can be complicated by autoimmune features associated with rheumatologic disorders, which have been commonly reported by more researches currently. The intrinsic correlation between CMML and autoimmune diseases can create significant pitfalls in differential diagnosis. CMML occasionally presents with clinical and histopathological manifestations that are similar to those of Immunoglobulin G4-related disease (IgG4-RD), a newly recognized systemic autoimmune disorder. Both CMML and IgG4-RD can have significant overlaps due to the common nature of these systemic disorders, especially when atypical clinical phenotypes are present. It is significant for physicians to accurately distinguish CMML and IgG4-RD because the therapy modalities could differ extremely between the two entities. Here we present a unique case of a 70-year-old female who had a condition that mimicked the onset of IgG4-RD not only in terms of clinical manifestations but also in serology and histopathology analyses. Following a series of rigorous examinations, this patient was ultimately diagnosed as having CMML. Herein, we discuss the aspects of IgG4-RD's differential diagnosis and the need for careful comparison of clinical and laboratory features as well as consideration of the pathogenesis of both IgG4-RD and CMML. We also stress a concept that the presence of autoimmune conditions cannot be the sole basis to exclude diagnosis of CMML, as these disorders can appear concomitantly.