We consider heavy quark production in high energy pA collisions and investigate the contribution of interactions of valence quarks of proton with the nucleus. The often made assumption that valence quarks of proton can be factored out is justified only if the nucleus saturation momentum is much smaller than the heavy quark mass. This is not the case in phenomenologically relevant situations. Breakdown of factorization manifests itself in substantial decrease of the cross section at large total and small relative transverse momenta of the heavy quark-antiquark pair.