The results of individual studies examining the role of p53 as a predictive and prognostic factor in lymphoid malignancies have varied considerably. In order to summarize the available data on the overexpression or mutation of p53 in Hodgkin's and non-Hodgkin's lymphoma, a systematic literature review was performed. Twenty-four studies met the eligibility criteria. With respect to non-Hodgkin's lymphoma, most studies seem to support the hypothesis that patients whose tumors contain wild-type p53 respond better to treatment and have increased survival rates. If true, the implication may be that patients with p53 mutated tumors could be selected for non-standard treatment. With respect to Hodgkin's lymphoma, comparable associations were rarely reported. However, techniques for assessing the inactivation of p53 varied widely. Furthermore, in most instances, the study design and/or statistical methods did not allow sufficient analyses of the influence of confounding factors such as histologic type, stage, first-line and salvage treatment, etc. Therefore, it remains unclear whether the apparent influence of p53 status on outcome in non-Hodgkin's lymphoma is independent of established parameters such as stage, performance status, etc. Further studies involving large numbers of specimens derived from patients treated in clinical trials with identical regimens, follow-up and salvage strategies are needed. These studies should also be stratified according to histologic subtypes.