The Epiphany Cathedral, one of the oldest churches in Tomsk, has a history that begins with a wooden church built in 1630. In 1858, a chapel in honor of the Iveron Icon of the Mother of God was constructed on the site of the altar of this church. The modern stone building of the cathedral in the Baroque style began construction in 1777. The lower floor was consecrated in 1784 in honor of the Epiphany of the Lord. Soon, a chapel dedicated to Archangel Michael appeared on the lower floor, while the upper floor housed the Ilyinsky and Spassky chapels.

The church plays an important role in the history of Tomsk. Since 1892, a charity for the poor operated at the cathedral, and from 1898, a church parish school was established. A library with 400 volumes of books also functioned here. Since the church is dedicated to the Epiphany, an annual procession to the Tom River for the Great Blessing of Water was held on January 19 for the Feast of the Baptism. Processions were also conducted on Pentecost and on the Feast of the First Savior.

The cathedral was closed for services in 1930, and courses for Sibzheldorstroy were opened within its walls. In 1936, a vermicelli factory was established here, and in 1942, the 'Krasny Bogatyr' factory was evacuated to this location. From 1947 to 1994, the Tomsk Rubber Footwear Factory operated in the building. In the second half of the 20th century, the church suffered greatly: domes and crosses were removed, the octagon of the bell tower was destroyed, new buildings were added, and the decor and shape of the windows on the southern facade were altered.

The restoration of the Epiphany Cathedral began in 1997 after its return to the Russian Orthodox Church in 1995. In 2000, daily services resumed in the church. A Sunday school, a youth club, and a community for the deaf operate at the cathedral.

The main relic of the church is a particle of the relics of Saint Great Martyr and Healer Panteleimon, brought from Moscow in 2001 by His Grace Rostislav.