Born Romona Parker in Brooklyn, the rap star rose to fame with a cameo in the 1988 song "Self Destruction" alongside Heavy D, MC Lyte and Kool Moe Dee.
She was also known for her mega singles, "Hype According to Ms. Melodie," "Live on Stage" and a memorable cameo in Queen Latifah's "Ladies First" video.
Her first and only album, Diva, was released in 1989 via Jive Records.
Ms. Melodie is the ex-wife of legendary rapper KRS-One, who produced much of her debut album. She was survived by two sons.
A cause of death has not been released.