Peptide-receptor radionuclide therapy (PRRT) with somatostatin analogs is an efficient new tool in patients with neuroendocrine tumors, with low risk of toxicity. Since lymphocytes express somatostatin receptors, the aim of this study was to evaluate lymphocytic toxicity after PRRT.From May 2005 to May 2007, 16 patients affected by neuroendocrine tumors received PRRT with (90)Y-DOTATOC (9), (177)Lu-DOTATATE (5), or both (2). Absolute count, percentage of leukocytes and lymphocytes, and lymphoid subsets (B, T, and NK) were tested at baseline and until 90 days after treatment.A significant lymphoid toxicity (G2-3), mainly affecting B-cells, was observed. It was particularly evident after (90)Y-DOTATOC. Toxicity resulted in being transient and resolved completely at the end of the follow-up (90 days).Lymphocyte toxicity in PRRT is mainly due to the selective targeting on B-cells. The relative sparing of T-lymphocytes could explain the absence of clinical side-effects in these patients, such as increased risk of infections. These findings open interesting perspectives in the treatment of B-cell lymphoproliferative disorders.