He was first named an assistant instructor in clinical surgery under J. William White, and then he ran the hospital's X-ray service, which seemed to combine his interests in photography and surgical problems.

Like many of the pioneers in radiography, Leonard suffered from adverse effects of radiation exposure before the causes of these problems were fully understood.

Before he died of radiation-induced cancer, Leonard had multiple operations, including the amputation of his entire right arm.

The family could trace its ancestry back to John Leonard, who left England in 1632 to settle in Springfield, Massachusetts, and to William Brewster, who came to the U.S. on the Mayflower.

[3]: 8–9 Leonard took a position as an assistant instructor of clinical surgery at Penn, where he worked under surgeon J. William White.

While he continued to do general X-ray work, he gained a wide reputation for his ability to diagnose kidney stones.

Two things likely contributed to this decision: a busy schedule of other professional responsibilities and the onset of disabling tissue injuries from radiation exposure.

Leonard developed X-ray burns and then radiation-induced cancer that started in a finger and eventually traveled up the entire arm and to other parts of his body.

At that time, he shared the belief of many physicians that X-ray burns were caused by a lack of grounding of the electrical current from the apparatus.

[3]: 14  In an 1898 article in the New York Medical Journal, Leonard described a patient with inoperable cancer who underwent 25-minute X-ray exposures every day for three weeks.

The surrounding areas were shielded with the aluminum sheet, and the patient sustained no X-ray burns (and received no therapeutic benefit).

[8]: 340 Leonard was so convinced of his electrical current explanation that for several years he did not take any precautions to shield his hands from radiation.

[4]: 1543  The problems with Leonard's hands worsened, and an already skeptical public most likely began to notice the injuries to his skin.

[3]: 14–15 During the final months of his life, Leonard spent much of his time collaborating with Austrian radiologist Guido Holzknecht on a review of radiography in gastrointestinal conditions that was to be read at the August 1913 meeting of the Section of Radiology of the International Congress of Medicine.

In spite of significant pain and suffering, Leonard read through literature in English, French and German in preparing the work.

[10] The American Roentgen Ray Society established the Charles Lester Leonard Prize to recognize outstanding contributions to X-ray technology.

[11] Leonard is buried in an unmarked grave near the conservatory at West Laurel Hill Cemetery in Bala Cynwyd, Pennsylvania.