Intra-articular administration of hyaluronic acid is a valuable therapeutic tool for the management of patients with osteoarthritis. However, in recent years numerous formulations containing hyaluronic acid administrable by oral route have entered the market. Even if there are some data in the literature that have shown their effectiveness, systemic administration may expose a greater risk in certain situations. In fact, although hyaluronic acid is not considered a drug it is certain that it can interact with specific receptors and promote cell proliferation. This interaction may be potentially hazardous in cancer patients for which these oral formulations should be contraindicated.