Chronic and localized plaque-type-psoriasis is often therapy resistant as a result of which dermatologists often have trouble finding a suitable treatment option. Traditional therapies for psoriasis merely focus on the inhibition of epidermal proliferation, inflammation, or both. The earliest changes, however, in a novel psoriatic lesion concern abnormal microvasculature. The position of lasers in the treatment of psoriatic lesions is debatable, as different views exist with respect to efficacy and tolerability. The current investigation evaluates the clinical and immunohistochemical effect of the Nd:YAG (1,064 nm) laser in chronic localized psoriasis, as this laser can penetrate up to the deeper abnormal psoriatic vasculature. The effects are compared to treatment with the well-established calcipotriol/betamethasone dipropionate ointment. The use of the Nd:YAG laser with treatment-intervals of four weeks was found not to be of additional value in the array of treatment modalities for chronic localized plaque-psoriasis. Targeting the more superficially located microvasculature in psoriasis seems of stronger significance for achieving a clinical effect than the deeper vasculature targeted by the Nd:YAG laser. Therefore, the present data are of importance in preserving dermatologists from treating psoriatic lesions with a Nd:YAG laser. However, further studies incorporating changes in methodology, in particular shortened time-intervals between treatments, are needed in order to refute or confirm this position.