Large/aggressive B-cell lymphomas are diverse both in terms of clinical presentations and treatment response. Diagnostic pathologic evaluation typically begins with a CD20/CD3 immunohistochemical panel. Prebiopsy steroid treatment has been reported to delay diagnosis and subsequent treatment due to altering histomorphology and immunohistochemical staining patterns. This study investigates the impact of prebiopsy steroid use on morphology and immunohistochemical staining patterns in large B cell lymphoma and/or mature B cell lymphomas with high Ki67 expression. Fourteen cases of B cell lymphoma treated with prebiopsy steroids and 13 cases of treatment-naive large B cell lymphoma and/or mature B cell lymphomas with high Ki67 expression were included in this study. Clinicopathological parameters, including type, dose, and route of steroid administration, were documented. Histopathologic slides from both groups were examined to assess morphology and immunohistochemical staining patterns. Morphologically significant effects attributable to steroid administration included significant histiocytic infiltrate and lack of diffuse pattern of infiltration of the lymphoma cells. The CD20 staining pattern, characterized by cytoplasmic/granular distribution and extracellular spillage, showed a statistically significant increase in the steroid group compared with the control group (P=0.011). This alteration was more prevalent among patients treated with intravenous dexamethasone, high-dose corticosteroids over a short term, and with shorter dosing intervals. Prebiopsy corticosteroid administration induces changes in histomorphology and immunohistochemical staining patterns, particularly affecting CD20, thereby posing diagnostic challenges. The extent of these effects varies depending on the type, route, dosage, and duration of steroid administration.