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Aims To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients. Methods and results The prognostic significance of immunohistochemical markers ( CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, Fox P1, LMO2) and algorithms ( Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco- Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R- CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival ( OS; P = 0.033, P = 0.010 and P = 0.008, respectively). High Bcl-2 (≥80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival ( PFS; P = 0.001, P = 0.048, P = 0.045 and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS ( P = 0.022, P = 0.037 and P = 0.011) and PFS ( P = 0.021, P = 0.020 and P = 0.004). The Choi, Choi* and Tally were associated with PFS ( P = 0.049, P = 0.009 and P = 0.023). In multivariate analysis, the International Prognostic Index ( IPI) was the only independent predictor of outcome ( OS; HR: 2.60, P < 0.001 and PFS; HR: 2.91, P < 0.001). Conclusions Results highlight the controversy surrounding immunohistochemistry-based algorithms in the R- CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized. [ABSTRACT FROM AUTHOR]