The series stars Laura Linney as Cathy Jamison, a suburban wife, mother, and teacher whose cancer diagnosis forces her to shake up her life.
The series co-stars Oliver Platt, John Benjamin Hickey, Gabriel Basso and Gabourey Sidibe.
Najimy will appear in all four episodes as Cathy's no-nonsense therapist, who will help her deal with the challenges she faces. Mizrahi, who will appear in several episodes as himself, will play a fashion mentor to Sidibe's character Andrea, who will start design school.
"It has been a true joy watching someone as gifted as Laura Linney take Cathy Jamison on her journey these past three seasons," David Nevins, President of Entertainment for Showtime Networks Inc., said in a statement. "We wanted to take particular care to honor the fans of the show with a compelling and memorable conclusion. We thank Laura, Jenny Bicks, Darlene Hunt, and 'The Big C's' gifted ensemble of actors, producers and crew for the remarkable work they have created."
"'The Big C' succeeded in exploring one woman's journey through cancer in a complex, thought-provoking and darkly comedic way and we're pleased that the story will have a dramatic conclusion with these final episodes," said Jamie Erlicht, president of U.S. programming and production for Sony Pictures Television. "We're proud of the awards and accolades 'The Big C' has received over the years and we congratulate these accomplishments by the producers, writers, crew and the extraordinary cast."