Background: Lactoferrin (LF), an iron-binding glycoprotein, has a multifunctional role in humans, specifically in the regulation of iron homeostasis, host defense against infections and inflammations, even if some experimental studies attributed others activities to LF, such as cellular differentiation, regulation growth, protection against cancer development and metastases. Methods: We performed herein an immunohistochemical analysis of LF in a cohort of primary and metastatic neoplasms occurred in the bone by using a monoclonal specific antibody. LF reactivity was quantified using an intensity-distribution (ID) score. Results: In primary bone tumours, LF immunostaining as whole was evident in 21/82 cases (25.60%), either benign or malignant. About bone metastatic lesions, LF immunopositivity was encountered in 14/30 cases (46.6%), mainly due to prostatic, renal, uterine and colonic carcinomas, while the positivity was reduced in metastases from breast carcinomas and it was completely absent in lung cancer. Conclusion: On the light of these results, we suggest that neoplastic elements might produce LF in order to make a greater amount of iron available for their turnover. Additional analyses are needed concerning new applications of LF in clinical oncology either for its nutraceutical function either for its capability to potentiate chemotherapy.