Pihos was born in 1923 in Orlando, Florida. His parents, Louis and Mary Pihos, were Greek immigrants. In August 1937, when Pihos was 13 years old, his father, the operator of an all-night restaurant in Orlando, was murdered. His body was discovered behind the counter of the restaurant with his skull fractured in 12 places.

Pihos was selected by the Philadelphia Eagles in the fifth round (41st overall pick) of the 1945 NFL Draft, but he continued to play for Indiana in 1945 and 1946. In February 1947, he signed to join the Eagles after his graduation in June. In his first NFL season, he caught 23 passes for 382 yards and seven touchdowns. He also blocked a punt by Sammy Baugh and returned it 26 yards for a touchdown against the Washington Redskins.  The Eagles made it to the NFL Championship Game in each of Pihos' first three seasons with the team. In 1947, the team captured its first division championship. In the playoff game against the Pittsburgh Steelers for the Eastern Division title, Pihos blocked a punt to set up the first touchdown in the Eagles' 21-0 win. The Eagles then lost 28-21 to the Chicago Cardinals in the 1947 NFL Championship Game. Pihos caught three passes for 27 yards in that game and intercepted a pass while playing defense. The Eagles then won consecutive NFL championship games in 1948 and 1949. Pihos scored the only offensive touchdown of the 1949 championship game via a 31-yard reception in the second quarter during a heavy downpour.  Pihos' 766 receiving yards and 11 receiving touchdowns in 1948 were both the second-most in the NFL that season. He earned first-team All-Pro recognition in 1948 from United Press (UP), New York Daily News, Chicago Herald-American, and Pro Football Illustrated and in 1949 from the International News Service, UP, Associated Press, and New York Daily News. He was invited to his first of six-straight Pro Bowls after the 1950 season. In 1951, Pihos led the Eagles in receptions and receiving yards and intercepted two passes as a defensive end.  Pihos caught only 12 passes and scored only one touchdown in 1952, causing the Eagles front office to suspect he was washed up. However, he still managed to make the Pro Bowl and earn first-team All-Pro honors by the AP as a defensive end. Not willing take a pay cut and be an exclusive defensive end, Pihos trained heavily during the off-season prior to 1953. He went on to have his greatest statistical success over the next three seasons, which were ultimately his final three; he recorded similar statistics over that three-year span (185 receptions, 2,785 yards, and 27 touchdowns) to his first six seasons (188 receptions, 2,834 yards, and 34 touchdowns). Pihos led the NFL in receptions in each of his final three seasons, in receiving yards twice, and in receiving touchdowns once. In 1953, he became the third different player to record a "triple crown" in receiving; he led the NFL in receptions (63), receiving yards (1,049), and receiving touchdowns (10) that season.  In November 1955, Pihos announced that the current season would be his last as a player. In his final NFL game, on December 11 against the Chicago Bears, he caught 11 passes for 114 yards. He retired after playing in the Pro Bowl that January, in which he caught four passes and scored the East's first touchdown by out-leaping defender Jack Christiansen to snag a 12-yard pass from Eddie LeBaron. During his nine seasons of play with the Eagles, Pihos missed just one game.

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did he set any records?