The primary plasma cell leukemia (PCL) is a rare aggressive plasma cell dyscrasia. We investigated its clinical and laboratory aspects in a large series of patients. Among 934 consecutive patients with multiple myeloma (MM), registered between 1978 and 2004 in a single institution, 30 patients [M/F: 22/8; median age (yr): 60, range: 36-79] with PCL (3.1%) were diagnosed. Retrospective analysis of the clinical, immunophenotypic, and cytogenetic aspects was performed. All patients had anemia, thrombocytopenia, circulating plasma cells (median count 4 x 10(9)/l), and in 18/30 patients hypercalcemia was found. Extramedullar involvement was present in 18/30 (60%) patients. The plasma cells were CD138+ and CD38+ (9/9), CD20+ (1/9), and CD10+ (1/9) with cytoplasmic positivity for light chains (9/9). The cytogenetic studies, evaluable in 21/30 patients, showed normal karyotype (6/21), complex hypodiploidy (6/15), pseudodiploidy (5/15), and hyperdiploidy (4/15). Treatment modalities had no impact on survival (median 4.5 months). Seven patients achieved remission. The performance status (ECOG >or= 2), platelet count <or= 100 x 10(9)/l, and serum LDH value >or= 460 U/l were independent prognostic parameters of survival. The immunologic and cytogenetic presentation of patients with PCL bears little significance on prognosis, which is heavily compromised by advanced age at diagnosis and the poor performance status.