Follicular lymphoma (FL) is a slow-growing B-cell lymphoma with a generally favorable prognosis. Nevertheless, its clinical course is heterogeneous, with a significant subset of patients experiencing early progression or histological transformation into diffuse large B-cell lymphoma (DLBCL), both considered to be high-risk events associated with treatment resistance and markedly inferior outcomes. Importantly, clinical risk factors have limited value in predicting these complications. This review outlines the key biologic features of FL, discussing how the novel molecular biology approaches can explain the clinical heterogeneity and high-risk disease evolution of FL.