Argentine forward German Cano's brilliant 73rd-minute solo effort gave visiting Medellin a 1-0 win at Envigado on Sunday.
Cano made it five goals in four games after cutting inside his defender, rounding the goalkeeper and scooping the ball into the net.
Medellin (29 points, +10) moved a point clear at the Clausura summit with two games remaining following defeat to Santa Fe (28 points, +11) and a stalemate for Once Caldas (28 points, +10).
Nelino Tapia's 45th-minute goal condemned Santa Fe to a 1-0 loss at second-bottom Uniautonoma on Saturday.
Once Caldas were forced to share the spoils on Sunday after playing out a goalless draw with sixth-placed Atletico Huila.
Deportivo Cali and Atletico Nacional both consolidated spots inside the top eight in their quest to reach the semi-finals.
Fourth-placed Cali came from behind to beat finals hopefuls Deportes Tolima 3-2 on Sunday.
Nacional - fifth in the table - scored two second-half goals as they accounted for Aguilas Pereira 2-0 on Saturday.
In other results, Leonardo Villagra's hat-trick inspired cellar-dwelling La Equidad to an emphatic 4-2 victory over Patriotas Boyaca.
Deportivo Pasto came from behind twice to earn a thrilling 3-3 draw at home to Junior.
Millonarios downed 10-man Alianza Petrolera 2-0, while Boyaca Chico drew 0-0 with Fortaleza.
