Azad Uddin, 30, rang his mother on Friday afternoon and said he was on his way back to his home in Lane Cove.
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A day later he has still not been seen or heard from and police are concerned for his welfare.
Police said Mr Uddin suffered from a medical condition and was last seen leaving his house on Longueville Road about 1.30pm.
He phoned his mother about 3.30pm but has not been heard from since.
Police have described him as Indian in appearance, clean shaven, about 165 centimetres tall and of medium build.
When he was last seen he was wearing a navy tracksuit jacket, black tracksuit pants and black sneakers.
Anyone who knows or has seen anything is urged to contact Crime Stoppers on 1800 333 000.
