Shakur and Madonna dated from 1993 to 1994, and the rapper's three-page confessional note to the singer, dated Jan. 15, 1995 with certain paragraphs blurred out, is going up for auction on the GottaHaveRockandRoll website on July 19.
Shakur died in 1996.
"For you to be seen with a black man wouldn't in any way jeopardize your career, if anything it would make you seem that much more open and exciting. But for me, at least in my previous perception, I felt due to my 'image' I would be letting down half of the people who made me what I thought I was," he wrote. "I never meant to hurt you."
Still, Shakur indicated that their relationship had had its ups and downs.
"An interview where you said 'I'm off to rehabilitate all the rappers & basketball players' or something to that effect ... cut me deep," he added. "I had never known you to be with any rapper besides myself."
The letter ends with the words, "I don't know how you feel about visiting me but if you could find it in your heart I would love to speak face to face with you."
A handwritten album track list from the rapper was sold on the site this past April for $3,000. The letter will have a starting bid of $100,000 and is expected to sell for triple or quadruple that amount.
ABC News has reached out to Madonna's rep for comment, but did not immediately receive a response.