This paper discusses the differential diagnosis of unusual and distinct pathological changes in the skeletal remains of a 40+-year-old female from 15th–20th century Coimbra (Portugal). The most affected area seems to have been the skull, but multiple lesions, lytic and/or blastic, have been found throughout the post-cranial skeleton, more specifically in the scapulae, clavicles, humerus, sternum, ribs, sacrum, innominates and femurs. The differential diagnosis of the lesions gave rise to several possible pathological conditions, namely, Langerhans cell histiocytosis (granulomatosis or Histiocytosis X), multiple myeloma and metastatic carcinoma. Various macroscopic and radiological aspects lead us to consider metastatic carcinoma as the most probable diagnosis. Despite the argumentative identity of the possible primary lesion, age, sex and the mixed nature of the osseous response are consistent with cancer of the breast but do not exclude other carcinomas, namely lung cancer. With temporal and regional differences emerging in the frequency of malignant tumours, the identification of new cases becomes important, particularly from geographic areas where few cases have been reported. In fact, the present report adds to the only case of metastatic carcinoma detected in non-identified Portuguese human skeletal remains until now. Copyright © 2009 John Wiley & Sons, Ltd.