Skin cancer is one of the most commonly diffused cancer in the world and its incidence rates have constantly increased in recent years. At the current state of the art, there is a lack of objective, quick and non-invasive methods for diagnosing this condition; this, combined with hospital crowding, may lead to late diagnosis. Starting from these considerations, this paper addresses the implementation of a microwave reflectometry based-system that can be used as a non-invasive method for the in-vivo diagnosis and early detection of biological abnormalities, such as skin cancer. This system relies on the dielectric contrasts existing between normal and anomalous skin tissues at microwave frequencies. In particular, a truncated open-ended coaxial probe was designed, manufactured and tested to sense (in combination with a miniaturized Vector Network Analyzer) the variations of skin dielectric properties on a group of volunteer patients. The specific data processing demonstrated the suitability of the system for discriminating malignant and benign lesions from healthy skin, ensuring simultaneously effectiveness, low cost, compactness, comfortability and high sensitivity.