Background: kappa and lambda light chains detection in bone marrow trephine sections help in the determination of B-cell clonality through evaluation of light chain restriction. Aim of the Work: was to compare the efficacy of single color detection-based immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in evaluating kappa/lambda expression in tissues harboring B-lymphoid lesions. Patients and Methods: Forty patients were enrolled in this study. They were divided into three groups chronic lymphocytic leukemia (CLL/SLL) group I (n=13), non-Hodgkin lymphoma (NHL) group II (n=24) and hairy cell leukemia (HCL) group III (n=3). The 24 NHL cases comprised of (11 diffuse large B-cell lymphoma, 6 mantle cell lymphomas, 3 marginal zone lymphoma, 2 lymphoplasmacytic lymphoma, 1 follicular lymphomas and 1 Burkitt's lymphoma). Kappa and lambda light chains were detected in their bone marrow trephine sections using single colored immunohistochemistry, chromogenic in situ hybridization and the results were compared to the flowcytometry as reference method. Results: Light chain restriction (LCR) was detected by FCM in 100% of the cases followed by CISH (52.1%; 12/23) of the cases and finally IHC (43%; 18/40). Background: kappa and lambda light chains detection in bone marrow trephine sections help in the determination of B-cell clonality through evaluation of light chain restriction. Aim of the Work: was to compare the efficacy of single color detection-based immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in evaluating kappa/lambda expression in tissues harboring B-lymphoid lesions. Patients and Methods: Forty patients were enrolled in this study. They were divided into three groups chronic lymphocytic leukemia (CLL/SLL) group I (n=13), non-Hodgkin lymphoma (NHL) group II (n=24) and hairy cell leukemia (HCL) group III (n=3). The 24 NHL cases comprised of (11 diffuse large B-cell lymphoma, 6 mantle cell lymphomas, 3 marginal zone lymphoma, 2 lymphoplasmacytic lymphoma, 1 follicular lymphomas and 1 Burkitt's lymphoma). Kappa and lambda light chains were detected in their bone marrow trephine sections using single colored immunohistochemistry, chromogenic in situ hybridization and the results were compared to the flowcytometry as reference method. Results: Light chain restriction (LCR) was detected by FCM in 100% of the cases followed by CISH (52.1%; 12/23) of the cases and finally IHC (43%; 18/40). Conclusion: Both conventional CISH and IHC are effective in determining monoclonality in cases of mature B- cell neoplasm that has plasmacytic differentiation and with high amount of cytoplasmic Ig light chains such as MZL and LP. However, they are not effective in determining monoclonality in cases with low amount of Ig light chain such as cases of pregerminal and germinal center lymphoma. Yet, CISH is more informative than IHC due to the lack of background staining which allowed for greater discrimination between absence and presence of monoclonality.