Publisher Summary This chapter summarizes the main findings of some recent immunohistochemical studies and relates Bcl-2 expression to clinicopathologic parameters, expression of proliferation or apoptosis-related proteins, and clinical outcome. The Bcl-2 gene was primarily investigated in hematologic malignancies and concretely in follicular B-cell lymphomas, where it contributed to tumorigenesis by preventing cell death. However, Bcl-2 overexpression was also found in lymphomas and other malignancies lacking the 14; 18 translocation. It has been suggested that this overexpression may prevent or delay normal cell turnover caused by apoptosis, thus prolonging cellular life span, which may increase the risk of secondary genetic alteration resulting in malignant transformation. Subsequent studies showed that high levels of the protein can suppress the initiation of apoptosis in response to a number of stimuli, including chemical oxidative injury, heat shock, ionizing radiation, and chemotherapeutic agents. However, the molecular function of Bcl-2 remains elusive.