Pholus differed sharply from the typical centaurs of myth. Whereas most were bestial descendants of Centaurus (himself the offspring of Ixion and the cloud Nephele), Pholus — like the tutor Chiron — was distinguished by civilized and gentle behaviour. Apollodorus makes him the son of Silenus and one of the Meliae, differentiating him genealogically from the common herd. That descent did not confer immortality: unlike Chiron, Pholus was mortal.

In art he sometimes shares the "human-centaur" form usually reserved for Chiron — a fully human body with the horse's midsection and hindquarters attached at the rear — which set both figures apart from centaurs shown as human only to the waist.

While Heracles was on his way to capture the Erymanthian Boar (the fourth labour), he was entertained in Pholus' cave on Pholoe. Apollodorus says Pholus set roast meat before his guest while eating his own meat raw. When Heracles asked for wine, Pholus feared to open the jar that belonged to the centaurs in common; Heracles opened it anyway. Scenting the wine, the neighbouring centaurs armed themselves with rocks and firs and stormed the cave.

Heracles drove off the first assailants with firebrands and shot the rest, pursuing the survivors as far as Malea, where they took refuge with Chiron. An arrow that passed through another centaur lodged in Chiron's knee; the Hydra venom made the wound incurable and led, in Apollodorus' sequence, to Chiron's eventual surrender of immortality. Meanwhile Pholus, back in his cave, drew an arrow from a corpse and wondered that so small a thing could kill such large creatures; the shaft slipped, struck his foot, and killed him on the spot. Heracles returned, found him dead, buried him, and then proceeded to the boar hunt.

Diodorus offers a related variant in which Pholus is wounded while preparing the dead centaurs for burial. Hyginus preserves a tradition that transfers the accidental arrow-wound from Pholus' foot to Chiron instead.

The Arcadian locality of Pholoe took its name from the centaur. In Dante's Inferno Pholus appears with the other centaurs who patrol the banks of the Phlegethon in the seventh circle of Hell, a medieval afterlife that keeps him in the company of his race rather than of Chiron the tutor alone.

Attic black-figure painters treated the hospitality and the ensuing fight as early as the sixth century BC. Surviving examples include a black-figured hydria of about 520–510 BC in the Louvre showing Heracles and Pholus, and a skyphos of about 580 BC with Heracles, Pholus, and the attacking centaurs.