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La introducción presenta a Isaac y su madre. Nos explica por qué Isaac huye y nos pone en contexto sobre el juego. La secuencia animada está narrada por el padre de Isaac, al cual le pone voz el propio Edmund McMillen.

Transcripción
A continuación se puede leer la transcripción del diálogo de la secuencia de introducción del título. El juego originalmente está disponible exclusivamente en inglés.

Isaac and his mother lived alone in a small house on a hill. Isaac kept to himself, drawing pictures and playing with his toys as his mom watched Christian broadcasts on the television. Life was simple, and they were both happy. That was, until the day Isaac’s mom heard a voice from above. “Your son has become corrupted by sin. He needs to be saved.” “I will do my best to save him, my Lord,” Isaac’s mother replied, rushing into Isaac’s room, removing all that was evil from his life. Again the voice called to her, "Isaac’s soul is still corrupt. He needs to be cut off from all that is evil in this world and confess his sins." “I will follow your instructions, Lord. I have faith in thee,” Isaac’s mother replied as she locked Isaac in his room away from the evils of the world.

One last time, Isaac’s mom heard the voice of God calling to her. “You've done as I have asked, but I still question your devotion to me. To prove your faith, I will ask one more thing of you." "Yes Lord, anything.” Isaac’s mother begged. "To prove your love and devotion, I require a sacrifice. Your son Isaac will be this sacrifice. Go into his room and end his life, as an offering to me to prove you love me above all else." "Yes Lord", she replied, grabbing a butcher’s knife from the kitchen.

Isaac, watching through a crack in his door, trembled in fear. Scrambling around his room to find a hiding place, he noticed a trapdoor to the basement hidden under his rug. Without hesitation, he flung open the hatch, just as his mother burst through his door and threw himself down, into the unknown depths below.

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