Both, Ishtori Haparchi and Rabbi Chaim Joseph David Azulai, make mention of him in their writings.

[7] Rabbi Isaac's commentary of Seder Zera'im has been printed in the 1890 Romm Wilna edition of the Babylonian Talmud.

[7] In Rabbi Isaac ben Melchizedek's commentary, besides citing from the two Talmuds, he frequently makes use of other classical rabbinic sources, such as the Tosefta, the Sifra on Leviticus, Sifrei Zuṭa on the Book of Numbers, the Aramaic Targum, the Seder 'Olam, the Sefer Arukh of Rabbi Nathan ben Jehiel of Rome, the commentary written by Rabbi Hai Gaon on the Mishnaic orders of Zera'im and Ṭaharot, as well as cites elements taken from R. Nissim's Sefer Mafteaḥ ("The book of the key to unlocking the Talmud").

Two manuscripts exist of Isaac ben Melchizedek's Mishnah commentary, one at the Bodleian Library in Oxford (no.

[Note 1] Rabbi Isaac's method of elucidating the Mishnah is concise, resembling that of Rashi's commentary on the Talmud.