TRPM8, a member of the melastatin-type transient receptor potential ion channel family, is activated by cooling agents. Exposure of TRPM8 to menthol or cold results in an increase in intracellular free Ca2+ ([Ca2+]i). Icilin is the most potent activator of TRPM8. We have some functional evidence that TRPs could be expressed in the human neuroendocrine tumor (NET) cell line BON. However, the role of TRPs in NET cells remains unknown. In this study, we investigated effects of menthol and icilin in a permanent model of NET cells (BON). The expression of TRPM8 was identified by RT-PCR and immunofluorescence staining. The effects of the cooling agents werde determined by fluorescence imaging and the patch-clamp technique. Icilin (300 nM) increased [Ca2+]i from 104 ± 8 nM to 185 ± 14 nM (recovery occurred to 120 ± 7 nM; n = 3; p < 0.01). In addition, cation channel currents increased from 19 ± 5 pA/pF to 43 ± 10 pA/pF (n = 8; p < 0.05). Furthermore, icilin regulated neurotensin secretion. The same results could be registered with menthol (100 mM) at lower levels. In conclusion, BON cells express functionally active TRPM8. Activation of TRPM8 leads to secretion of neurotensin from BON cells. Potentially, TRPM8 may play a role in pathophysiology and/or therapy of NETs.