The amphisbaena is a two-headed lizard or serpent. It has one head in the normal position, and another at the end of its tail. Because its heads point in opposite directions it can run in either direction without needing to turn. Gaius Julius Solinus and Isidore of Seville say that when the two heads both try to lead, the amphisbaena moves in a circle or with its body trailing in a loop behind both heads. Both heads eat fish and pass the nourishment to their common body. Its eyes shine like lamps, and it has no fear of cold.

The amphisbaena is usually depicted as a dragon-like beast having wings and two feet, with horns on its head. There is always a second head on the end of its tail, usually smaller than the other head, which is attached to the front of a body. In some illustrations there is no distinction between head and tail; the amphisbaena is depicted as a snake with an equal-sized head at either end, and only a thin snake body between. In many cases the "primary" head is shown biting the neck of the head on the tail.

The name "amphisbaena" is now given to a legless lizard that can move either forward or backward, though this is a relatively modern use of the name.