Two time-domain fluorescence imaging techniques have been developed and tested for the detection of malignancies after administration of a marker having a fluorescence lifetime longer than that of the tissue natural fluorescence. The first technique, based on the time-gated approach, relies on the acquisition of fluorescence images after a suitable delay with respect to the excitation pulses in order to discriminate the long living exogenous fluorescence from the short living endogenous one. The second technique, called lifetime imaging, measures the spatial map of the fluorescence decay time of the sample, allowing an indirect detection of the regions where the concentration of the marker is higher. The first method is simpler, does not require any image processing, leading to a true real time video, but it works better when a rather strong signal comes from the sample. The second method requires two or more images to be acquired and processed sequentially; therefore, it is slower, but proved to be more sensitive in low signal conditions. The two techniques have been applied for the detection of skin tumors in humans after the topical application of (delta) -aminolevulinic acid ointment, which promotes the accumulation of the endogenous porphyrin Protoporphyrin IX preferentially in proliferative tissues. Preliminary results are encouraging.