33 patients with indolent lymphoma and 51 with aggressive lymphoma received Cop. FL (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. 80 patients were evaluated for efficacy. The OR rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort. Median PFS was 294 days (range 0–874) and 70 days (range 0–897), respectively; median duration of response was 390 days (range 0–825) and 166 days (range 0–786), respectively. Molecular analyses showed enhanced anti-tumor activity in tumors with enhanced PI3K pathway gene activation. Here, PIK3CD is linked to aggressive behavior.