The differential diagnosis of tumors at the base of the skull comprises meningiomas, neurinomas, gliomas, metastatic carcinomas, chordomas, epidermoids, and pituitary adenomas. About half of the pituitary adenomas are prolactinomas which are unique in a sense that medical therapy causes rapid tumor shrinkage and symptomatic improvement. We report on two patients in which the diagnosis of an invasive macroprolactinoma was masked by apparently low prolactin levels caused by a high-dose hook effect in the chemiluminometric assay. The first case a 49 year old male with impairment of hearing on the left side was presented in the Department of Otorhinolaryngology. A massive invasively growing tumor was demonstrated on a cranial MRI. Endocrine tests revealed normal pituitary function and normoprolactinemia. The patient underwent debulking surgery, occipitocervical fusion because of destruction of the first cervical vertebra and subsequent irradiation. The histopathological diagnosis was invasive prolactinoma. A repeat prolactin (PRL) sample, which was assayed using serial dilutions, revealed a real PRL level of 89,700 ng/ml. Dopamine agonist therapy was initiated under which PRL levels declined in parallel with tumor size. The second case a 40 year old male was presented with acute visual loss. Cranial MRI showed a large tumor at the base of the skull. Based on a transnasal biopsy, the preliminary diagnosis was a poorly differentiated carcinoma for which emergency irradiation was performed. Endocrine tests demonstrated partial hypopituitarism and moderate hyperprolactinemia. Hydrocortisone was substituted and dopamine agonist therapy was started because of moderate hyperprolactinemia. The final histopathological diagnosis was invasive prolactinoma. A repeat PRL sample assayed in serial dilution demonstrated an apparent rise in PRL with a maximum value of 6,460 ng/ml. Under dopamine agonist therapy, PRL declined to normal values, tumor size decreased and cranial nerve palsies disappeared. The apparently falsely low prolactin levels in the initial work-up of both patients were caused by a high-dose hook effect in the PRL assay. Serial dilutions of serum PRL samples is, therefore, mandatory in the diagnostic work-up of patients with large invasive tumors at the base of the skull. This avoids unnecessary aggressive and dangerous treatment like surgery or radiotherapy in cases where pharmacological treatment may be the choice.