Among clinically relevant somatostatin functions, agonist-induced somatostatin receptor subtype 2 (sst2) internalization is a potent mechanism for tumor targeting with sst2 affine radioligands such as octreotide. Since, as opposed to octreotide, the second generation multi-somatostatin analog SOM230 (pasireotide) exhibits strong functional selectivity, it appeared of interest to evaluate its ability to affect sst2 internalization in vivo. Rats bearing AR42J tumors endogenously expressing somatostatin sst2 receptors were injected intravenously with SOM230 or with the [Tyr3, Thr8]-octreotide (TATE) analog; they were euthanized at various time points; tumors and pancreas were analyzed by immunohistochemistry for the cellular localization of somatostatin sst2 receptors. SOM230-induced sst2 internalization was also evaluated in vitro by immunofluorescence microscopy in AR42J cells. At difference to the efficient in vivo sst2 internalization triggered by intravenous [Tyr3, Thr8]-octreotide, intravenous SOM230 did not elicit sst2 internalization: immunohistochemically stained sst2 in AR42J tumor cells and pancreatic cells were detectable at the cell surface at 2.5min, 10min, 1h, 6h, or 24h after SOM230 injection while sst2 were found intracellularly after [Tyr3, Thr8]-octreotide injection. The inability of stimulating sst2 internalization by SOM230 was confirmed in vitro in AR42J cells by immunofluorescence microscopy. Furthermore, SOM230 was unable to antagonize agonist-induced sst2 internalization, neither in vivo, nor in vitro. Therefore, SOM230 does not induce sst2 internalization in vivo or in vitro in AR42J cells and pancreas, at difference to octreotide derivatives with comparable sst2 binding affinities. These characteristics may point towards different tumor targeting but also to different desensitization properties of clinically applied SOM230.