Background: Essential thrombocythemia (ET) with Primary Myelofibrosis (PMF) and finally Polycythaemia Vera (PV), are considered the three main entities of the Philadelphia-negative MPNs. Mutations in JAKII, together with CALR and Myeloproliferative Leukemia Protein (MPL) genes can be detected in most of cases with Philadelphia-negative MPNs. The discovery of CALR mutations was implicated in better understanding of the molecular mechanisms involved in the pathogenesis of MPNs patients who had no mutations in JAKII or MPL genes. Patients and methods: The current study included 56 participants diagnosed with MPNs. Bone marrow trephine biopsy (BMB) was the sample of choice in our study. CALR specific monoclonal antibody (CAL2) by IHC was done for all MPN patients on BMB specimens. Results:  Nearly 82 % of our cases (46/56) were positive for CALR mutation by IHC with sensitivity of 96.4%, and specificity of 88.9%, with positive predictive value of 94.7%, while negative predictive value was 92.3%, and total accuracy of CALR was 93.9%. We found a significant association between JAKII mutation and CALR positive patients (p=0.004) hyper cellular marrow was prevailing in CALR positive patients (p= 0.004). In addition, CALR mutant patients were associated significantly with higher degrees of fibrosis grade III & IV (p= 0.044). However, no significant relation between splenomegaly and CALR positivity was detected in our study. Conclusion: CAL2 by IHC was a sensitive and specific marker in detecting CALR mutation in patients diagnosed as MPN. Moreover, it was readily available and cost effective than other routine molecular techniques used in detecting such mutation.