According to the most recent global cancer statistics, the burden of malignancies continues to increase worldwide, so that there is a compelling need to reinforce the screening strategies and implement novel diagnostic approaches for early detection. Canines are widely used by police forces and civilian services for detecting explosives and drugs due to their superior olfactive apparatus, which is characterized by a detection threshold as low as parts per trillion. There is mounting evidence that dogs might be effectively trained to detect patients with various form of cancers due to the presence of a characteristic “odor signature”. In particular, preliminary studies reported that appropriately trained dogs exhibit an extraordinary ability to detect melanoma as well as prostate, breast, ovary and lung cancers by recognizing a characteristic “odor signature” in body, urines, sweat, breath and even blood. The most problematic issue that has emerged so far is the large heterogeneity of performance across the different studies as well as within the same study, which might be dependent upon genetic characteristics or training methodology. This article is aimed to provide an overview of the available data on cancer sniffer dogs, highlighting the appealing perspectives and the potential drawbacks.