Background: Mycosis fungoides (MF) represents the commonest form of cutaneous T-cell lymphoma. MF is usually diagnosed on clinico-pathological bases. Treatment regimens for MF include skin-directed therapies such as PUVA, topical chemotherapy, topical rexinoids and total skin-electron beam radiation. To treat patients with MF adequately the physician often needs to take multiple biopsy specimens of clinically highly suggestive lesions to follow up the response to therapy. This can be a significant burden for the patients, so a non-invasive technique would therefore be of great value. Fluorescence diagnosis with 5-aminolevulenic acid (5- ALA) as a topical photo-sensitizer is gaining interest in an increasing number of dermatological centers. In this technique the preferential accumulation of endogenous porphyrins, in particular proto-porphyrin IX (PPIX) in lesional skin after incubation with ALA is used to diagnose various skin diseases. Objective: To detect the efficacy of fluorescence diagnosis as a simple and non-invasive tool in follow-up of MF patients during the course of therapy.Methods: This study was carried out for 12 weeks. Twenty two MF patients receiving different types of phototherapeutic modalities were included. Each patient was subjected to fluorescence diagnosis after three hours application of 5-ALA on the mostly affected skin lesion followed by 5mm punch skin biopsy from the same lesion. The punched skin biopsy was processed and then subjected to flow cytometric analysis. After 12 weeks of therapy the same procedures were repeated.Results: There was a significant decrease in the values of accumulation factor (AF), the percent of CD4+ve/CD7-ve T-cells and the percent of the total count of T-cells (% gated) before and after therapy. There was a negative correlation between the severity of the disease and the degree of clinical response of skin lesion which was statistically significant. There was a positive correlation between AF difference and the degree of clinical response of the disease. No correlation was detected between the AF and the percent of the malignant T-cells estimated by the flow cytometry (%CD4+ve/CD7-ve cells) before and after therapy. When comparing the clinical severity, degree of clinical response, results of fluorescence diagnosis and flow cytometry (FCM) to the stage of MF disease, no significant results were detected.Conclusion: In cases of MF, FD can represent a prognostic tool for evaluating the response to therapy. Changes in accumulation factor values can be used for follow-up of therapy in the same patient, as it parallels changes in clinical response. It should not be used as an absolute value. FD is to be used for patches and plaques of MF and not for nodules or tumors, until further studies on large patient numbers are performed.