He studied medicine at the Universities of Berlin, Bonn and Strasbourg, and in 1876 earned his medical doctorate. Later he became an assistant to Oskar Simon (1845-1892) at the dermatological clinic in Breslau, and in 1882 received his habilitation at the University of Leipzig. In 1892 he was an associate professor at the University of Bonn, and in 1896 was appointed chief physician of the syphilitic department at the Berlin-Charité. The following year he became head of the dermatological and syphilitic dispensary at the University of Berlin.
Lesser was a leading authority in the field of syphilis research. He was the author of Lehrbuch der haut- und geschlechtskrankheiten für studirende und ärzte (Textbook of Skin and Venereal Diseases for Students and Physicians) which ran for numerous editions and was included in Adolph Strümpell's Lehrbuch der speciellen Pathologie und Therapie der inneren Krankheiten. Also, with zoologist Richard Hertwig (1850-1937), he was co-author of Über Rhizopoden und denselben nahestehende Organismen. Other publications by Lesser include: