Mel first appears in The Late Dr. Crane when Niles confronts her (after initially believing that she was male) when he continued to receive bills for Maris' surgeries after they had divorced. Unable to master enough courage to ask her out, Niles pretends to be interested in some botox treatment for himself. Eventually, Niles does ask her out for a date and they begin a relationship soon afterwards.
She is much like Niles (and Maris) in demeanor and personality, but continues to push him in a wrong direction (as she is like Maris). It's mentioned that she is divorced and has an adult son, but his name is never stated; however Niles remarks that he is middle-aged, indicating that Mel is much older than she looks but simply had a lot of plastic surgery herself.
In The Fight Before Christmas, Niles and Mel briefly break up after Frasier lets it slip that Niles had a meeting with Maris to console her over the loss of a friend. However, the two reconcile at the end of the episode.
In Whine Club, Frasier schedules a brunch at his apartment to get better acquainted with Mel. However, Mel stirs the pot between Frasier and Niles when she suggests that he run against his brother for "corkmaster" of their local wine club. Niles ends up winning and Frasier initially takes the defeat in stride until he finds out that it was Mel's idea to have Niles run. This revelation ends up bringing out a collective dislike for Mel among the rest of the group as Daphne, Roz and Frasier tell Niles as such. Despite this, Niles still dismisses them and continues seeing her.
In Something Borrowed, Someone Blue: Part 1, Niles and Mel impulsively elope while out of town, just days before Daphne and Donny's wedding. They intend to keep the marriage quiet (so as not to upstage Daphne and Donny) but Daphne finds out about the marriage anyway. In the following episode, the marriage falls apart when Niles finally confesses his love for Daphne.
After Niles runs off with Daphne, Mel is left humiliated and bitter. As payback, Mel refuses to grant Niles an immediate divorce and forces him to participate in a charade of happy marriage for the sake of appearances until an appropriate time, after which she will file for divorce. However, it soon becomes apparent that Mel is intentionally prolonging the divorce process to ensure maximum humiliation of Niles
In Taking Liberties, Mel shows up unannounced at a party hosted by Frasier at his apartment. This pushes Niles over the edge and he confronts her, publicly disowning the “sham of a marriage” in the process. Mel, escorted by her friends who insult Niles, leaves hurt and defeated and is never seen again.