Bob Marley died in 1981 at the age of 36. He was diagnosed with acral lentiginous melanoma (ALM), a rare and aggressive form of skin cancer, in 1977. The cancer was first noticed as a dark spot under his toenail, which he attributed to a soccer injury. If the cancer had been detected early, it could have been treated and possibly cured. However, Marley did not seek treatment early enough, and the cancer spread to other parts of his body, including his brain and lungs, leading to his death.

Marleys final words to his son Ziggy were "On your way up, take me up. On your way down, dont let me down". He died at Cedars of Lebanon Hospital in Miami on May 11, 1981, due to the spread of melanoma to his lungs and brain.