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The Giallorosse travel to face the Serie B side on Saturday afternoon, with the return leg taking place later in the month.
After reaching the semi-finals last season, coach Betty Bavagnoli is eager for her side to go even further this time around.
"The Coppa Italia is crucial, we are focused on this competition and want to go as far as we possibly can," Bavagnoli said.
"We come into the game in good shape, with the right approach. We've worked hard on our mentality recently and in the last two games I think there's been an improvement in that regard."
Roma come into the game having beaten Pink Bari in the last-16, while San Marino Academy stunned Verona to move into the quarter-finals.
"I don't really think about favourites," Bavagnoli added.
"It's a tough opponent - San Marino are building something impressive, and they are doing well in Serie B. Our girls need to be aware that it won't be an easy game - they absolutely have to be focused.
"The tie will be played out over 180 minutes and we are making sure the players are all ready for it. The players have shown that they are able to cope with changes to the line-up, because all the girls are ready to play.
"I want all my players to believe in the qualities they bring."
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