We retrospectively analyzed overall survival and survival after progression in 91 patients with low-grade follicular lymphoma (LGFL). Histological subtype was B in 75 patients and C in 16 patients. Twelve patients with localized disease received involved-field radiotherapy; seven patients without bulky disease had no initial therapy. The remaining 72 patients received long-term chlorambucil (9 patients), MOPP or COPBleo (42 patients), or a CHOP-derived regimen (21 patients). Forty-two patients (46%) achieved a complete remission (CR) and 28 patients (31%) achieved a partial remission; 48 of these 70 patients relapsed or progressed. Nineteen of the other 21 patients with stable LGFL progressed. Two other patients failed to respond and rapidly died. Thirty-two of the 67 patients with progressive or relapsed LGFL have died. Median overall survival was 111 months. Age > or = 70 years, male sex, B symptoms, histological subtype follicular mixed-cell NHL, tumor size > or = 10 cm, number of extranodal sites of disease > or = 2, pleural effusion, and Ann Arbor stage III or IV were found to adversely influence overall survival. Failure-free survival < 24 months, failure to achieve a CR after the progression, initial histological subtype follicular mixed cell, initial Ann Arbor stage III or IV, and initial tumoral size > or = 10 cm were found to adversely influence survival after progression. Our results suggest that most prognostic factors for overall survival in LGFL are related to histological subtype or tumor burden. Some initial adverse prognostic factors for survival may be also associated with a poor survival after progression.