Our long-term activity in the development of fluorescence imaging for the detection of early superficial bladder cancer aimed at optimizing the selective production and accumulation of photoactivable porphyrins (PaP), mainly protoporphyrin IX (PpIX), after the instillation of derivatives of aminolevulinic acid (ALA) within cancerous tissues. This research eventually led to the approval of hexylaminolevulinate (HAL, Hexvix(R)) in 27 European countries. Although the selective production of PpIX and the sensitivity of this procedure are outstanding, its specificity is limited due to false positive lesions that are mainly associated with inflammations of the bladder mucosa. Therefore, our current research focuses on the improvement of the specificity of this detection method. New methods, using high magnification (HM) endoscopy, are being investigated by our group in order to discriminate false from true positive findings, and hopefully resulting in a reduced number of biopsies. In this study, we are using a dedicated magnification cystoscope, allowing conventional magnification during "macroscopic" white light and fluorescence observation, as well as image acquisition with HM when the endoscope is in contact with the tissue. This is realized by an optical setup directly integrated in the cystoscope. The diameter of the field of view of the images is 500 microns in the HM mode and the resolution is about 3 microns. With this optical setup, our on going study is aimed at observing and characterizing the neo*-vascularization of the flat fluorescing sites in order to distinguish (pre-)cancerous tissue from inflammation. Thirty nine biopsies were taken on fluorescence-positive sites. The vascular patterns observed on CIS (n = 7) were significantly altered in 5 of them (71%), as compared to normal and inflamed mucosa where such alterations were never observed.