Dyspnea is one of the most common symptoms in the clinical setting, the main causes being represented by respiratory and cardiovascular disorders but sometimes it is difficult to identify and document the underlying mechanism of breathlessness. We present the case of a 75-years-old male patient, former smoker, with progressive worsening dyspnea. He performed a complex imagistic, respiratory, and functional assessment, the results showing severe emphysema with mild obstructive syndrome, in contrast with severe impairment of diffusing capacity of the lung for carbon monoxide (DLCO) due to inhomogeneous distribution of ventilation/perfusion ratio. This case brings to front a certain type of chronic obstructive pulmonary disease (COPD), with suggestive clinical exam but with minimal impairment of spirometry results in the presence of debilitating dyspnea. In order to perform an accurate diagnosis, alternative functional diagnostic measurements, like estimation of DLCO, should be used.