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Background: There is an increasing interest in TRPM8 ligands of medicinal interest, the rational design of which can be nowadays supported by structure-based in silico studies based on the recently resolved TRPM8 structures. <b>Methods</b>: The study involves the generation of a reliable hTRPM8 homology model, the reliability of which was assessed by a 1.0 &#956;s MD simulation which was also used to generate multiple receptor conformations for the following structure-based virtual screening (VS) campaigns; docking simulations utilized different programs and involved all monomers of the selected frames; the so computed docking scores were combined by consensus approaches based on the EFO algorithm. <b>Results</b>: The obtained models revealed very satisfactory performances; LiGen&#8482; provided the best results among the tested docking programs; the combination of docking results from the four monomers elicited a markedly beneficial effect on the computed consensus models. <b>Conclusions</b>: The generated hTRPM8 model appears to be amenable for successful structure-based VS studies; cross-talk modulating effects between interacting monomers on the binding sites can be accounted for by combining docking simulations as performed on all the monomers; this strategy can have general applicability for docking simulations involving quaternary protein structures with multiple identical binding pockets.