Background: Disseminated superficial actinic porokeratosis (DSAP) is characterized by asymptomatic multiple papules with annular keratotic rim distributed symmetrically on the sun-exposed areas. Many approaches have been proposed in the past for treating DSAP, but the therapy is still a challenge for every physician, mostly because of the frequent relapses of the disease and the multiplicity of the skin lesions. Material and Methods: Two case reports were reported emphasizing the challenges of treatment approach. Therefore, a systemic English literature review was conducted searching Medline database using PubMed Central and Ovid software as search interface to collect evidence based on the various treatment modalities for DSAP. Results: The initial search yielded 146 articles, but only the relevant case reports, case series and studies relating to the treatment of DSAP have been described and summarized in a table. For each different therapy the efficacy of each treatment, side effects, cost-effectiveness and authors’ recommendations were reported. Conclusion: Several factors need to be considered prior to physicians’ decision of the most appropriate treatment for each patient like age, the extent of body surface area involvement, patients’ medical history and social situation, the available resources, the side effects and cost- effectiveness of each treatment. However, l the exact value of each treatment is difficult to determine owing to the lack of controlled studies evaluating their efficacy. Due to few incidences of squamous cell carcinoma, patients need to be followed up and monitored closely for any early detection of recurrence or possible onset of malignancies.