Vladimir Marin's opener was cancelled out by Gustavo Bolivar as Medellin were held to a 1-1 draw by 10-man Cali at the Estadio Olimpico Pascual Guerrero.
Medellin - needing victory in order to stay top of the Clausura standings after Santa Fe beat Boyaca Chico earlier on Sunday - hit the front courtesy Marin in the 40th minute.
Cali hit back almost immediately, Bolivar equalising on the stroke of half-time.
Andres Perez was sent off for a second bookable offence with three minutes remaining.
The result saw Medellin end the weekend in second position with 23 points from 12 games, one ahead of Cali.
Santa Fe, meanwhile, are one point clear at the summit.
Wilder Medina and Luis Arias were both on target as Santa Fe came from behind to beat Boyaca Chico 2-1.
Boyaca Chico took a 45th-minute lead through Winston Giron but Santa Fe hit back with two unanswered goals in the second half.
Once Caldas are third in the table following their goalless draw at Atletico Nacional.
Fernando Uribe scored four goals as Millonarios routed fellow strugglers Fortaleza 4-1.
Uribe netted in the first half and added three after the interval as Millonarios recorded their first win since July.
Envigado accounted for 10-man Junior 1-0, Neider Morantes' 64th-minute penalty the difference.
Deportes Tolima were the only other team to win over the weekend, downing Aguilas Pereira 2-0.
In other results, basement side La Equidad and Atletico Huila drew 1-1.
Second-bottom Uniautonoma played the final 18 minutes with 10 men but still earned a 1-1 draw at home to Deportivo Pasto.
Alianza Petrolera and Patriotas Boyaca also drew by the same scoreline.
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