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Objective To investigate the expression of PTEN and Caspase-3 in malignant lymphoma of the stomach and explore their role in progression of primary gastric malignant lymphoma. Methods Formalin-fixed paraffin embedded tissues from 56 cases of primary gastric malignant lymphoma and their adjacent non-tumor mucosa were evaluated for PTEN and Caspase-3 protein expression by streptavidin-biotin-complex (SABC) immunohistochemistry. Their expression was compared with clinical tumor parameters with the relationship between PTEN and Caspase-3 expression concerned as well. Results The positive rate of PTEN expression in primary gastric lymphomas (50.0%, 28/56) was significantly lower than that in adjacent non-tumor gastric mucosa (96.4%, 27/28) (P ＜ 0.05). Meanwhile,43 of 56(76.8%) gastric lymphomas indicated Caspase-3 expression, less than that in adjacent nontumor mucosa (93.5%, 29/31) (P ＜ 0.05). The expression of PTEN was negatively correlated with invasion and lymph node metastasis of gastric lymphoma (P ＜ 0.05), while the Caspase-3 expression was negatively associated with the latter one (P ＜ 0.05). Additionally, the PTEN expression was positively correlated with Caspase-3 expression in the primary gastric malignant lymphoma (P ＜ 0.05). Conclusions The down-regnlated expression of PTEN and Caspase-3 played an important role in progression of primary malignant gastric lymphoma. PTEN, as a molecular marker of pathobiological behaviors of tumor, contributes to tumor progression by increasing cell mobility and angiogenesis, as well as decreasing cell adhesion and apoptosis.