Background: The present study emphasizes the important role of newer hematological variables generated by Automated Cell Counters (ACCs) in early diagnosis and monitoring the response to the treatment in hematological malignancies and infections Aims: To evaluate the clinical applications of newer hematological parameters for expanding their diagnostic potential in cases of hematolymphoid malignancies and infections Study design: This cross sectional observational prospective study was conducted in the Department of Laboratory Sciences & and Molecular Medicine at a “Tertiary Care Super–Speciality Hospital” of North India Subjects & methods: EDTA blood samples of 40 & 10 cases of hematolymphoid malignancies and infections respectively were collected at pre and post treatment stages over a period of 18 months. The results obtained by ACCs and microscopic examination were compared Statistical Analysis Used: The hematological, parameters obtained from ACCs/microscopic were assessed by Student’s t–test, chi–square test (or Fisher’s exact test) using the SPSS 21.0 software with considering p value < 0.05 as significant Results: Immature Granulocytes (IGs) have potential role to predict sepsis and results obtained by ACCs and manual examination showed statistically significant relationship (p value< .05) IGs, Large unstained cells, WBC count from the Peroxidase channel were markedly raised in sepsis & hematolymphoid malignancies and exhibited a downward trends following effective therapy. ACCs have limitation to accurately evaluate % blast suspected in cases of leukemia as compared to PBS, however this issue can be overcome due to inherent flagging property of ACCs to atypical cells which hint the manual examinations of such samples.