Reaching the bottom of these regular Mines grants the Skull Key, which unlocks the Skull Cavern mines located in the Calico Desert. A quest given in a Secret Note by the mysterious Mr. Qi tasks players with reaching Level 100 of Skull Cavern in return for a reward.

In Stardew Valley, the initial "Skull Cavern" quest is triggered once you reach the bottom of the regular Mines (Floor 120) and obtain the Skull Key. Once you have the key, you must repair the Bus to the Calico Desert—either by completing the Vault bundles in the Community Center (42,500G) or purchasing the repair through the Joja Development Form (40,000G). After the bus is fixed, you can enter the Skull Cavern in the northwest of the Desert. A follow-up quest, "Qi's Challenge," is triggered the day after your first visit to the cavern; you will receive a letter in the mail from Mr. Qi challenging you to reach Floor 25. Later in the game, after finding Secret Note #10, you will trigger the quest to reach Floor 100, where Mr. Qi himself will be waiting to congratulate you and reward you with "Iridium Snake Milk" to permanently increase your health.